Archives of Medical Science
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2020
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IF 2.807
Ning Xu,Lili Wang,Shiping Fu,Bin Jiang
Introduction Osteosarcoma is the most common primary malignancy of the bone. The existing adjuvant chemotherapy regimens, while improving the overall survival, have been limited by the significant systemic toxicity. Substantial clinical and research efforts are being invested to develop novel pharmaceutical agents. Resveratrol (Res) has been suggested to have a chemopreventive effect. However, the mechanism of Res in osteosarcoma remains to be elucidated. Material and methods The MG-63 osteosarcoma cell culture model was used to investigate the chemotherapeutic effect of Res. MTT assay, wound healing assay, and Transwell migration assay were used to document the effect of Res on cell proliferation, migration, and invasion, respectively. Apoptosis in MG-63 cells was quantified with the TUNEL assay. Western blotting analysis was used to examine the molecular changes following Res treatment. Data processing and analysis were conducted using GraphPad Prism 5.0. P < 0.05 was considered statistically significant. Results Our data suggested that Res blocks cell proliferation, migration, and invasion, and activates apoptotic cell death in osteosarcoma MG-63 cells. We found that Res potentially down-regulates nuclear factor κB (NF-κB) and Akt intracellular signaling transduction. Moreover, the combination of Res and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, resulted in synergistic growth inhibition of osteosarcoma. Conclusions Our in vitro preclinical study in the MG-63 cell line model supports the translation of Res to the clinical management of patients with osteosarcoma.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
DRUG DELIVERY
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2018
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IF 3.095
Wei Wu,Yong Dai,Han Liu,Ruoyu Cheng,Qing Ni,Tingjun Ye,Wenguo Cui
Osteosarcoma is among the most common malignant bone tumors in human skeletal system. The conventional treatment of osteosarcoma mainly consists of combining neoadjuvant chemotherapy with surgical approach. However, it is crucial to design an artificial implant that possesses excellent biomechanical properties and is capable of sustaining local release of chemotherapeutics. In this study, we envision that the highly efficient combination of gemcitabine (GEM) hydrochloride loaded liposomes with gelatin methacryloyl (GelMA) of in situ photocrosslinkable hydrogel will lead to a multifunctional implant with unique antitumor, mechanical, and biodegradable properties. A sustained controlled release was observed; more specifically, the release of GEM in vitro lasted for 4 days long. Furthermore, its capability in killing MG63 cells was further explored by using the lixivium of GEM-Lip@Gel and GEM-GelMA hydrogel in vitro (composite hydrogel by GEM loaded liposomes blending with GelMA, short for GEM-Lip@Gel), which agreed with the drug release outcome. In addition, these hydrogel showed excellent ability in inhibiting osteosarcoma in vivo by Balb/c mice bearing MG63 cells. Therefore, GEM-loaded lipo-hydrogel certainly has presented itself as a promising strategy for the development of implant in the field of osteosarcoma treatment.
研究领域:
生物医学工程
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药剂学
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癌症研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2015
·Vol. 13
·期 1
·1-11
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IF 4.115
Wang Bing,Yu Xiu-Chun,Xu Song-Feng,Xu Ming
Background The combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma.Results The resulting drug-loaded PLGA NP exhibited a nanosize dimension with uniform spherical morphology. The NP exhibited a sustained release profile for both PTX and ETP throughout the study period without any sign of initial burst release. The combinational drug-loaded PLGA NP enhanced the cytotoxic effect in MG63 and Saos-2 osteosarcoma cell lines, in comparison to either native drug alone or in cocktail combinations. Additionally, NPs showed an appreciable uptake in MG63 cells in a time-based manner. Co-delivery of anticancer drugs resulted in enhanced cell cycle arrest and cell apoptosis. The results clearly showed that combinational drugs remarkably improved the therapeutic index of chemotherapeutic drugs. The greater inhibitory effect of nanoparticle combination would be of great advantage during systemic cancer therapy.Conclusion Taken together, our study demonstrated that PTX-ETP/PLGA NP based combination therapy holds significant potential towards the treatment of osteosarcoma.
研究领域:
肿瘤学
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药学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Jie Cao,Xiaoxuan Du,Hui Zhao,Chenhong Zhu,Chenchen Li,Xin Zhang,Libin Wei,Xue Ke
Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs) are thought to be the major cause of failure in cancer therapy due to their considerable resistance to most chemotherapeutic agents, resulting in tumor recurrence and eventually metastasis. Here, we report a treatment strategy for osteosarcoma using hydrogel−microspheres (Gel−Mps) complex mainly composed of collagenase (Col) and PLGA microspheres (Mps) carrying Pioglitazone (Pio) and Doxorubicin (Dox). Col was encapsulated in the thermosensitive gel to preferentially degrade tumor extracellular matrix (ECM), ensuring subsequent drug penetration, while Mps with Pio and Dox were co-delivered to synergistically inhibit tumor growth and metastasis. Our results showed that the Gel−Mps dyad functions as a highly biodegradable, extremely efficient, and low-toxic reservoir for sustained drug release, displaying potent inhibition of tumor proliferation and subsequent lung metastasis. Selective PPARγ agonist Pio reversed drug resistance to Dox by significantly down-regulating the expression of stemness markers and P-glycoprotein (P-gp) in osteosarcoma cells. The [email protected] @Dox/Pio exhibited advanced therapeutic efficacy in vivo , demonstrating its great potential to serve a novel osteosarcoma therapy, which not only inhibits the growth of, but also attenuates the stemness of osteosarcoma. The dual effects reinforce the sensitivity and efficacy of chemotherapy.
研究领域:
药理学
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肿瘤学
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生物材料科学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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2023
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IF 5.1
Ziyuan Tong,Yuan Shen,Quan Yuan,Honghao Yu
Despite recent advances in understanding the biological behavior of osteosarcoma (OS), OS is still the most common primary bone sarcoma that endangers the health of children and adolescents. High-temperature requirement A (HTRA) protease family plays an important regulatory role in numerous malignancies and acts as a prognostic biomarker. However, the function and underlying mechanisms of the HTRA family in OS development remain unknown. Through analyzing the GSE126209 dataset obtained from different Gene Expression Omnibus (GEO) databases, we found that HTRA3 as a member of the HTRA family was downregulated in OS tissues compared with that in normal tissues. Functional experiments indicated that HTRA3 overexpression suppressed malignant behaviors of OS cells in vitro and tumor growth in vivo . Mechanistically, we found that HTRA3 co-localized with the X-linked inhibitor of apoptosis protein (XIAP) and decreased XIAP stability. Further investigation showed that XIAP knockdown inhibited the degradation of phosphatase and tensin homolog (PTEN) and that HTRA3 caused the blockage of PTEN/phosphoinositide 3-kinase (PI3K)/AKT pathway, characterized as the reverse of cell function caused by HTRA3 overexpression after PTEN inhibitor BpV (HOpic) treatment. Detailed investigations showed that forkhead box protein 1 (FOXP1), an oncogene in OS progression, downregulated HTRA3 expression and inhibited the transcriptional activity of HTRA3 , suggesting that HTRA3 was regulated negatively by FOXP1. In conclusion, our study demonstrates that HTRA3 is a repressor involved in OS development via the PTEN/PI3K/AKT pathway under the modulation of transcription factor FOXP1, and it may provide a therapeutic direction for OS patients.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Cancer Nanotechnology
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2023
·Vol. 14
·期 1
·1-21
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IF 5.7
Wang Hongsheng,Jin Xinmeng,Gao Yinghua,He Xin,Xu Yiming,Mu Haoran,Jiang Yafei,Wang Zhuoying,Yu Chen,Zhang Tao,Hua Yingqi,Cai Zhengdong,Xu Jing,Ma Xiaojun,Sun Wei
Background Tumor angiogenesis, immunosuppression, and progression are all closely correlated with the tumor microenvironment (TME). Immune evasion is supported by both M2 phenotype tumor-associated macrophages (TAMs) and vascular aberrations in the TME. TME reprogramming is a promising therapeutic approach for treating tumors. Anti-angiogenesis has the power to control the polarization of macrophages, prevent progression, and increase drug penetration. Additionally, polyamine blocking therapy can increase CD8 + T cell infiltration and decrease immunosuppressive cells. These results led to developing a potential therapeutic regimen that targets TAMs and angiogenesis to reprogram the osteosarcoma TME. Results For the targeted biomimetic co-delivery of regorafenib and alpha-difluoromethylornithine via the mannose receptor, which is overexpressed in both TAMs and osteosarcoma cells, mannosylated poly(lactide-co-glycolide)-polyethylene glycol nanoparticles (Man-NPs) were synthesized. The superior physiological properties and intratumoral accumulation of the Man-NPs efficiently promoted TAMs polarization and inhibited angiogenesis. Macrophage repolarization further activated immune cells, which contributed to remodeling the TME. Conclusion Overall, these findings suggested that using Man-NPs as an immunotherapeutic approach to treat osteosarcoma may be promising. Graphical Abstract
研究领域:
肿瘤学
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药学
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免疫治疗
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纳米技术
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Hang Wu,Lei Xie,Shige Wang,Tengbo Yu,Yingze Zhang
High recurrence rates after surgery and unacceptable side effects of chemotherapy and radiotherapy are challenges in the treatment of osteosarcoma (OS). Therefore, the development of nanoplatforms with combined tumor inhibition efficiency and fewer side effects is a promising strategy for the treatment of OS. In this paper, a biocompatible therapeutic nanoplatform ( [email protected] @GOx) was constructed with a simple and efficient strategy for the treatment of OS. First, as an excellent Fenton reaction reagent, iron ions in the nanoplatform can generate highly toxic hydroxyl radicals (•OH) with hydrogen peroxide (H 2 O 2 ) in the tumor microenvironment and induce tumor cell death. Then, the modification of polydopamine endows the nanoplatform with photothermal responsiveness, with a photothermal conversion efficiency of 28.0%. Importantly, the conversed heat by polydopamine both promotes the release of glucose oxidase (GOx) and increases the rate of the Fenton reaction. Furthermore, GOx-mediated starvation treatment (SDT) can also provide suitable reaction conditions and sufficient H 2 O 2 to realize the amplification of chemodynamic therapy (CDT). Finally, the doping of Zr ions can interact with Fe to form dual active centers in the Fenton reaction and further accelerate the generation of •OH. Both in vitro and in vivo experiments reveal the synergistic photothermal/CDT/SDT anti-tumor effect. Therefore, this work provides an effective strategy for the treatment of OS.
研究领域:
癌症治疗
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纳米医学
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化学工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Chao Xie,Qili Sun,Jingle Chen,Bingsheng Yang,Huiwen Lu,Zhanpeng Liu,Yucong Li,Kai Li,Bin Tang,Lijun Lin
Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion–coordinated Tremella fuciformis polysaccharide (TFP–Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu 2+ release profile in smart response to tumor microenvironment stimulation. TFP–Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP–Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP–Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP–Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.
研究领域:
生物材料学
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肿瘤学
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免疫学
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骨再生医学
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产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2019
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IF 4.462
Jingwei Zhang,Yu Miao,Weifeng Ni,Haijun Xiao,Jieyuan Zhang
Photothermal therapy (PTT) is a rapidly developing approach for cancer therapy, which has been widely recognized to exert high efficacy as compared to chemotherapy. However, the limited tumour homing property of currently available drug delivery systems (DDSs) is the bottleneck for the efficient delivery of photothermal agents. Here in this study, we surface modified silica nanoparticles (SLN) with the cell membrane (CM) derived from 143B cells to construct a platform (CM/SLN) capable of targeting the homogenous 143B cells. In addition, indocyanine green (ICG) as a photothermal agent was encapsulated into CM/SLN to finally construct a DDS suitable for tumour-targeted PTT of osteosarcoma. Our results revealed that CM/SLN/ICG was mono-dispersed core-shell nanoparticles with advanced stability in a physiological environment. Moreover, due to the modification of CM, CM/SLN/ICG could specifically target the homogenous 143B cells both in vitro and in vivo, which demonstrated superior anticancer efficacy when compared with either SLN/ICG or free ICG. Hence, CM/SLN/ICG could be a promising DDS for tumour targeted PTT of osteosarcoma.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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药学
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DOI
PubMed
高影响因子
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
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2020
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IF 2.074
AiJun Huang,LiPing Chen,YiMing Wang,ShuQiang Ma,Song Jin,Hanzhou Cai,Xingzhong Huang,Hongbo Zhang,ZengRong Wang,Kun Lin,Fangsiyu Lin
Background:5-fluorouracil (5-FU) is a widely used drug for cancer treatment, but its effect and underlying mechanisms on osteosarcoma (OS) cells remain unclear.Methods:U2OS and MG63 cells were treated with 0, 50, 100, and 500 μM 5-FU. MTS and flow cytometry were used to examine the effect of 5-FU on cell viability and apoptosis, respectively. Circular RNA (circRNA) expression was detected using RNA sequencing and quantitative real-time PCR (qPCR). Differentially expressed circRNAs were further subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to predict their functions. A circRNA–miRNA–mRNA interaction network was generated to analyze the regulatory networks of 5-FU–induced differentially expressed circRNAs. Western blotting (WB) was used to verify the protein in the downstream of circRNAs.Results:5-FU inhibited the cell viability of the MG63 cells in a concentration-dependent manner. The most significant effect was observed in the cells treated with 500 μM 5-FU. Apoptosis was also increased in the MG63 cells after 500 μM 5-FU treatment for 3 days. RNA sequencing results showed that 183 differentially expressed circRNAs (172 upregulated and 11 downregulated) in 5-FU–treated cells. KEGG and GO analysis showed that the differentially expressed circRNAs were primarily enriched in proliferation-, apoptosis-, and metabolism-related functions. qPCR was used to verify the most upregulated and downregulated circRNAs. The circRNA–miRNA–mRNA interaction network showed that these 8 circRNAs had a sizable regulatory network that links a series of genes involved in tumor suppression.Conclusion:5-FU treatment resulted in the differentially expressed circRNAs that were proliferation- and apoptosis-associated and were involved in the 5-FU–induced inhibition of tumor proliferation in OS cells.
研究领域:
肿瘤学
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分子生物学
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基因组学
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癌症治疗
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF CANCER
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2024
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IF 5.7
Jiaxin Ren,Cheng Zhao,Ruizhu Sun,Jian Sun,Laiya Lu,Jun Wu,Shuaijun Li,Lei Cui
Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three-dimensional model of osteosarcoma constructed by seeding tumor cells (MG-63 and MNNG/HOS Cl no. 5) within demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG-63 and MNNG/HOS Cl no. 5 cell lines as compared to two-dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted in a decrease in drug resistance of osteosarcoma, which could be restored by α-ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance. What's new? Osteosarcoma resistance to chemical drugs remains poorly understood. Here, the authors constructed a novel three-dimensional osteosarcoma model by seeding tumor cells within demineralized bone matrix scaffolds. Growing within the scaffold conferred elevated doxorubicin resistance to osteosarcoma cells when compared to two-dimensional cultures. Osteosarcoma cells in demineralized bone matrix scaffolds displayed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism. This model could help better understand the complex cell–matrix interactions between osteosarcoma cells and surrounding native bone and potentially screen novel effective chemotherapies to treat osteosarcoma.
研究领域:
肿瘤学
·
细胞生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
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IF 8.758
Jie Yin,Qiuyang Han,Junchuan Zhang,Yunxiu Liu,Xueqi Gan,Kenan Xie,Lu Xie,Yi Deng
After an osteosarcoma resection, the risks of cancer recurrence, postoperative infection, and large bone loss still threaten patients’ health. Conventional treatment relies on implanting orthopedic materials to fill bone defects after surgery, but it has no ability of destroying residual tumor cells and preventing bacterial invasion. To tackle this challenge, here, we develop a novel multifunctional implant (SP@MX/GelMA) that mainly consists of MXene nanosheets, gelatin methacrylate (GelMA) hydrogels, and bioinert sulfonated polyetheretherketone (SP) with the purpose of facilitating tumor cell death, combating pathogenic bacteria, and promoting osteogenicity. Because of the synergistic photothermal effects of MXene and polydopamine (pDA), osteosarcoma cells are effectively killed on the multifunctional coatings under 808 nm near-infrared (NIR) irradiation through thermal ablation. After loading tobramycin (TOB), the SP@MX-TOB/GelMA implants display robust antibacterial properties against Gram-negative/Gram-positive bacteria. More importantly, the multifunctional implants are demonstrated to have superior cytocompatibility and osteogenesis-promoting capability in terms of cell replication, spreading, alkaline phosphatase activity, calcium matrix mineralization, and in vivo osseointegration. Accordingly, such photothermally controlled multifunctional implants not only defeat osteosarcoma cells and bacteria but also intensify osteogenicity, which hold a greatly promising countermeasure for curing postoperative tissue lesion from an osteosarcoma excision.
研究领域:
材料科学
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生物医学工程
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骨科
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肿瘤学
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传染病学
✓ 已验证
DOI
PubMed
高影响因子
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