Anti-Cancer Agents in Medicinal Chemistry
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2022
·Vol. 22
·期 18
·3172-3181
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IF 2.527
Xie Xiaoliang,Li Yumei,Zhu Haixia,Chen Lin,Chen Deta,Lin Shengming,Fan Tianyou
Background and Purpose: Osteosarcoma is the most commonly seen type of primary malignant bone tumors in children and adolescents. Partial patients with osteosarcoma cannot tolerate the side effects of chemotherapy drugs. Hence, it is urgent to find anti-osteosarcoma drugs with low side
effects. Melittin is an anti-tumor Traditional Chinese Medicine with low side effects. The purpose of this study was to explore the anti-osteosarcoma effect of melittin and its possible molecular mechanisms. Methods: The effects of melittin on cell growth were detected by CCK-8, clonal
formation, and flow cytometry. The related molecules were also investigated by Real-time PCR and Western blot. A xenograft model in nude mice was established to observe the effects of melittin on tumor growth and the related molecular expression was detected by immunohistochemistry. Results:
Melittin can inhibit the proliferation of osteosarcoma 143B cells, reduce colony formation, and induce apoptosis while significantly up-regulating the expression of Bax and Caspase-3 and down-regulating the expression of Bcl-2 proteins. Moreover, treatment with melittin significantly reduced
the mRNA and protein levels of β-catenin and Wnt/β- catenin related genes (LRP5, c-Myc, and Survivin) in osteosarcoma 143B cells in vitro. The xenograft model found that melittin significantly inhibited tumor growth and decreased the protein expression levels of β-catenin and
Wnt/β- catenin related genes in vivo. Conclusion: These findings show that melittin could inhibit the growth of osteosarcoma 143B cells, which may be related to the inhibition of Wnt/β-catenin signaling pathway activity and induce apoptosis by up-regulating the ratio of Bax/Bcl-2
in osteosarcoma 143B cells. Therefore, melittin is a promising anti-tumor drug for the treatment of osteosarcoma.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 6.5
Jiaoyan Liu,Ronghua Tan,Congcong Wang,Guimin Li,Hong Zheng,Ying Wan
Purpose The repair and reconstruction of bone defects resulting from tumor-related bone resection surgery face significant challenges. Developing biomaterials with dual functions of tumor therapy and bone regeneration is a promising strategy for osteosarcoma treatment.Methods and Results In this study, gallium-doped bioactive glass nanoparticles (GaBG NPs) with Ga contents of 5–15 mol% were synthesize and integrated into thiolated chitosan (CS-NAC) and silk fibroin (SF) composites to fabricate hydrogels systems for post-surgical bone repair applications. The optimized hydrogel system exhibited good injectability with a gelation time of approximately 4 min, moderate mechanical strength (> 3 kPa), high porosity, and sustained release of Si, Ca, and Ga ions within physiologically safe levels. In vitro, studies demonstrated that the GaBG-embedded hydrogels remarkably advanced the proliferation and osteogenic differentiation of MC3T3-E1 cells, while significantly inhibiting the growth of UMR-106 osteosarcoma cells, with the 15GaBG/CNS hydrogel reducing cell viability to <5% at 72 h. In a rat model of critical-sized calvarial defects, new bone formation reached 55 ± 8% of defect area after 8 weeks without additional cells or growth factors. Moreover, an osteosarcoma model in nude mice confirmed that the 15GaBG/CNS hydrogel significantly suppressed tumor growth without inducing detectable adverse effects in major organs.Conclusion These findings indicate that the developed GaBG/CNS composite hydrogels possess considerable potential for simultaneous bone regeneration and osteosarcoma inhibition.
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DALTON TRANSACTIONS
·
2026
·
IF 3.3
Guorui Song,Jinke Ji,Changying Li,Jinlong Zhao,Bo Zhang
Photodynamic therapy (PDT) has shown good therapeutic results in recent years, but the efficacy is limited by the hypoxic environment within cancer cells. At present, most of the research studies on overcoming PDT hypoxia focus on providing exogenous oxygen, but the effect is not outstanding. This work shows an unconventional source of free radicals, compared with the traditional PDT strategy of generating reactive oxygen species, using a radical polymerization initiator (2,2′-azobis (2,4-dimethylvaleronitrile), ABVN) to generate alkyl radicals, which is free from the limitation of oxygen, is simpler and more efficient, and has obvious therapeutic effects. By synthesizing hollow mesoporous manganese dioxide (MnO2) as a carrier, the nanoparticles are loaded with ABVN and encapsulated with PEG, which have excellent photothermal properties, can quickly heat up to the thermal decomposition temperature of ABVN under laser irradiation, can degrade and release ABVN in GSH and acidic environments, and generate a large number of alkyl radicals in a short period of time, with excellent treatment efficiency. This study breaks through the limitation of PDT caused by hypoxia in cancer cells and provides a promising research strategy for PDT treatment.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Enyang Yao,Yang Li,Kai Deng,Wei He,Milad Ashrafizadeh,João Conde,Liyu Yang
Osteosarcoma is the most common primary bone tumor with a high metastatic rate. Despite the improvement in patient prognosis with conventional therapeutics, enhancing the survival of patients with metastatic disease remains a challenge. Zoledronic acid (ZOL) stimulates apoptosis in cancer cells and is considered a promising drug for osteosarcoma therapy. Moreover, depletion of Inhibin Subunit Beta A (INHBA), a member of the transforming growth factor superfamily, can suppress osteosarcoma cell proliferation and invasion. Regarding the restricted potential of monotherapy, combination therapies, such as small interfering RNA (siRNA) and chemotherapy, are ideal strategies. However, off-target effects and adverse impacts lead to unsatisfactory clinical efficacy of these drugs. To address this challenge, we designed a folic acid-modified macrophage membrane coated with a carbon quantum dot (CQD) nanoplatform for the co-delivery of ZOL and siINHBA (ZOL-siINHBA@CQD@RM-FA). The anticancer activity of this nanotherapeutic agent was examined in vitro and in vivo . ZOL-siINHBA@CQD@RM-FA was approximately 200.7 nm in size, had a negative charge, excellent pH responsiveness, desirable biocompatibility, and high cellular uptake. This nanosystem achieved favorable co-delivery of ZOL/siINHBA and impaired osteosarcoma proliferation and invasion in vitro . Notably, intravenous administration facilitated tumor growth regression and inhibited lung metastasis without systemic toxicity. Accordingly, this nanotherapy could be considered an effective treatment for osteosarcoma, and the nanodelivery system shows potential for combined therapy by co-delivering genes and chemotherapy drugs.
研究领域:
肿瘤学
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纳米医学
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药物递送系统
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高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-19
·
IF 7.5
Xing Chunyang,Hu Wei,Zhao Liyuan
Background Osteosarcoma (OS) is one of the most common malignancies arising in bone. Hypoxia and immune regulation are pivotal in tumor biology. However, their combined effects and mechanisms in OS remain understudied. This study aimed to explore the role and mechanism of hypoxic-induced M2 macrophages in promoting the progression of OS.Methods Differentially expressed proteins in hypoxic macrophage supernatants were detected by antibody array. Cell functional experiments, siRNA-mediated gene silencing, and overexpression transfection were used to study osteopontin (OPN) and its supernatant effect. Bioinformatics analysis was applied to investigate downstream targets and pathways, and a xenograft model was established to assess in vivo effects.Results Our data revealed that hypoxic M2 macrophage supernatant enhanced OS malignancy and epithelial-mesenchymal transition, activating cancer pathways. Hypoxia upregulated OPN in M2 macrophages, and OPN inhibition reduced its tumor-promoting effect. Early growth response 3 (EGR3) was differentially expressed in OS cells treated with the supernatant, and its overexpression inhibited OS cell migration, reversing tumor promotion. Interferon-stimulated gene 15 (ISG15), a key differentially expressed gene related to OPN and EGR3 overexpression, inhibited OS cell proliferation and migration. Additionally, OPN increased retinoic acid-inducible gene I (RIG-I) expression and enhanced signal transducer and activator of transcription 3, nuclear factor kappa B, and extracellular signal-regulated kinase signaling, while EGR3 and ISG15 overexpression inhibited these effects. Silencing ISG15 restored pathway activation and reversed the inhibitory effect of EGR3 on OS cell migration. Dual-Luciferase reporter gene assay confirmed that EGR3 activates ISG15 transcription. OPN treatment upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression, and ChIP assays demonstrated that EGR3 overexpression enhanced DNMT1 binding to the EGR3 promoter. These findings suggest that OPN promotes OS malignancy by downregulating EGR3 and ISG15, and by enhancing RIG-I expression, as validated in a xenograft model of OS.Conclusion Our findings demonstrate that hypoxic-induced M2 macrophages promote OS progression through OPN-dependent mechanisms, including inhibition of EGR3 and ISG15 expression and upregulation of RIG-I.Graphical abstract
研究领域:
癌症生物学
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免疫学
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分子生物学
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细胞生物学
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肿瘤微环境
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信号转导
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Yulong Jin,Quan Li,Kai Tang,Yongmin Mao,Hang Zhang,Bo Zhang,Kai Wang,Aiguo Zhang
In cancer biology, cysteine (Cys) is pivotal in maintaining the redox balance within tumor cells. To explore alterations in Cys concentration within osteosarcoma (OS) and hepatocellular carcinoma (HCC) cells, we devised a novel fluorescent (FL) probe named JYL-Cys , utilizing a thiol-sensitive dye, which specifically reacts with Cys to emit FL at 718 nm (λ ex = 660 nm). JYL-Cys exhibits a high response fold, a low limit of detection (0.15 μM), high selectivity, and effectively detects Cys under physiological conditions. A comprehensive suite of in vitro experiments, encompassing cell uptake studies and FL imaging analysis, was executed to assess the responsiveness of JYL-Cys across various cancer cell lines, specifically the OS cell line MG-63 and the HCC cell line HepG2. Furthermore, in vivo mouse model experiments were conducted to validate the probe's applicability and safety in live organisms. The probe demonstrated exceptional capability in visualizing the distribution of Cys within both OS and HCC cells through imaging, revealing markedly elevated Cys levels compared to normal cells. Notably, in vivo experiments confirmed the probe's safety for biological applications. Our experimental findings underscore that JYL-Cys is a valuable resource for delineating the biological significance of Cys in cancer progression and establish a foundation for future clinical applications, encompassing early diagnosis and prognosis assessment.
研究领域:
癌症生物学
·
生物成像
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分子探针
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生物化学
·
诊断成像
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高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Guangyu Jian,Si Wang,Xinlu Wang,Qinyi Lu,Xingyu Zhu,Shucheng Wan,Shan Wang,Dize Li,Chao Wang,Qingqing He,Tao Chen,Jinlin Song
Background Osteosarcoma (OS) is a malignant tumor originating from primitive mesenchymal cells, characterized by rapid metastasis, high invasiveness, and significant mortality. The primary challenges in OS management include the effective elimination of residual tumor cells to prevent recurrence and the repair of extensive bone defects caused by surgical intervention. Objective This study aims to develop an innovative biomimetic 3D-printed bioactive glass ceramic (BGC) scaffold modified with two-dimensional nanosheets to address both tumor ablation and bone tissue repair. Materials and methods The nanosheets were constructed via ellagic acid (EA) and ruthenium (Ru) coordination, leveraging the non-topological adhesion properties of catechol in EA to deposit the nanosheets onto the BGC scaffold (EARu-BGC). The therapeutic effects of EARu-BGC were evaluated in vitro and in vivo . Results EARu-BGC sequentially responds to the local microenvironment during OS treatment. During the tumor ablation phase, EARu-BGC induced ferroptosis through the synergistic effects of photothermal and chemodynamic therapy, achieving over 90 % tumor cell ablation and significantly inhibiting tumor volume and weight. In the bone tissue repair phase, EARu-BGC exhibited adaptive ROS scavenging and facilitated a pro-healing microenvironment, promoting osteogenic differentiation. The gradual degradation of the BGC scaffold provided essential minerals and space for new bone formation. In vivo experiments demonstrated that EARu-BGC significantly enhanced osteogenesis, increasing the trabecular number to 1.51 ± 0.15/mm and reducing trabecular separation to 1.50 ± 0.04 mm. Conclusion The EARu-BGC scaffold presents a promising multifunctional platform for OS treatment by effectively balancing antitumor efficacy with bone repair capabilities.
研究领域:
生物医学工程
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肿瘤学
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再生医学
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高影响因子
ACTA BIOCHIMICA POLONICA
·
2021
·Vol. 68
·期 4
·725-732
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IF 2.149
Ziyan Wu,Zhong Zhou,Weiguo Zhang,Yi Yu
MicroRNA (miR)-21 has been found to be overexpressed in osteosarcoma (OS). The aim of the present study was to investigate the effect of miR-21-5p on the Warburg effect and stemness maintenance in OS cells and its potential molecular mechanism. Herein, miR-21-5p was overexpressed or inhibited in MG-63 cells via transfection with mimics or inhibitors. The effect of miR-21-5p on cell viability, apoptosis, Warburg effect and stemness maintenance were explored in OS cells. The results demonstrated that miR-21-5p inhibition suppressed MG-63 cell viability and enhanced their apoptosis. Additionally, miR-21-5p inhibition attenuated the stemness maintenance of MG-63 cells, as demonstrated by the reduced proportion of CD133-positive MG-63 cells, the decrease in tumorsphere formation capacity, and the downregulation of Sox2, Oct4, and Nanog proteins. Moreover, miR-21-5p inhibition suppressed the Warburg effect in MG-63 cells, as indicated by the decrease in glucose uptake, lactic acid production, and ATP level and the downregulation of proteins involved in the Warburg effect (GLUT1, LDHA, HK2, and PKM2). Furthermore, the results suggested that the effect of miR-21-5p suppression on stemness and the Warburg effect may be associated with the decreased activity of the Wnt/β-catenin pathway in OS cells. Our findings suggest a novel potential biomarker for OS therapy.
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Biomaterials Science
·
2023
·
IF 6.6
Ruijia Han,Yajun Min,Guanlin Li,Shilu Chen,Maobin Xie,Zheng Zhao
Concurrent treatment of tumor recurrence and bone defects after surgical resection of osteosarcoma remains a clinical challenge. Combination therapy based on local drug delivery systems shows great promise in the treatment of osteosarcoma. In this study, curcumin modified polydopamine nanoparticle loaded silk fibroin doped with nano-hydroxyapatite (CM-PDA/SF/nHA) nanofibrous scaffolds were developed to induce bone defect regeneration and chemo-photothermal synergistic effects against osteosarcoma. These scaffolds exhibited good photothermal conversion efficiency and photostability. Moreover, the results of ALP staining and alizarin red S (ARS) staining indicated that the CM-PDA/SF/1%nHA scaffolds had the most obvious promotion effect on early osteogenic differentiation. The results of in vitro and in vivo anti-osteosarcoma activity showed that the CM-PDA/SF/1%nHA scaffolds exhibited higher anti-osteosarcoma activity compared to the control and SF scaffolds. In addition, the CM-PDA/SF/1%nHA scaffolds could promote the proliferation and differentiation of bone marrow mesenchymal stem cells in vitro and new bone production in vivo. Thus, these results suggested that the CM-PDA/SF/1%nHA scaffolds could improve bone defect regeneration and achieve chemo-photothermal synergistic effects against osteosarcoma.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-20
·
IF 10.2
Yu Kexiao,Zhou Hang,Xu Yamei,Cao Youde,Zheng Yuanyi,Liang Bing
Malignant bone tumors result in high rates of disability and death and are difficult to treat in terms of killing tumors and repairing bone defects. Compared with other hyperthermia strategies, magnetic hyperthermia has become an effective therapy for treating malignant bone tumors due to its lack of depth limitations. However, tumor cells express heat shock protein (HSP) to resist hyperthermia, which reduces its curative effect. Competitive ATP consumption can reduce HSP production; fortunately, the basic principle of starvation therapy by glucose oxidase (GOx) is consuming glucose to control ATP production, thereby restricting HSP generation. We developed a triple-functional magnetic gel (Fe 3 O 4 /GOx/MgCO 3 @PLGA) as a magnetic bone repair hydrogels (MBRs) with liquid‒solid phase transition capability to drive magneto-thermal effects to simultaneously trigger GOx release and inhibit ATP production, reducing HSP expression and thereby achieving synergistic therapy for osteosarcoma treatment. Moreover, magnetic hyperthermia improves the effect of starvation therapy on the hypoxic microenvironment and achieves a reciprocal strengthening therapeutic effect. We further demonstrated that in situ MBRs injection effectively suppressed tumor growth in 143B osteosarcoma tumor-bearing mice and an in-situ bone tumor model in the rabbit tibial plateau. More importantly, our study also showed that liquid MBRs could effectively match bone defects and accelerate their reconstruction via magnesium ion release and enhanced osteogenic differentiation to augment the regeneration of bone defects caused by bone tumors, which generates fresh insight into malignant bone tumor treatment and the acceleration of bone defect repair.
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
IF 3.9
Tang Zhouzhou,Li Zhihao,Wu Guofeng,Li Jianjun,Tan Jianye,Zhu Lixin
Osteosarcoma (OS) is the most common primary malignant bone tumor. Recent evidence suggests that the novel long noncoding RNA DHRS4 antisense RNA 1 (DHRS4-AS1) serves an important role in cancer progression and metastasis. However, its function and molecular mechanism in OS remain largely unknown. In the present study, DHRS4-AS1 expression was detected in OS cells by quantitative PCR. Gain- and loss-of-function experiments were conducted to study the effects of DHRS4-AS1 on the proliferation and apoptosis of OS cells. The potential mechanism of DHRS4-AS1 was examined through bioinformatics analysis and rescue experiments. DHRS4-AS1 was downregulated in OS cell lines. DHRS4-AS1 depletion promoted proliferation and inhibited apoptosis in OS cells, whereas DHRS4-AS1 overexpression had the opposite effects. Further research suggested that DHRS4-AS1 inhibited OS progression by regulating the microRNA-362-5p/aminopeptidase puromycin sensitive axis. The present findings suggested that DHRS4-AS1 may serve as a potential therapeutic target for OS.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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高影响因子
Nanoscale
·
2021
·Vol. 13
·期 9
·5077-5093
·
IF 7.79
Zhou Sha,Shuguang Yang,Liwen Fu,Mengru Geng,Jiani Gu,Xuying Liu,Shikai Li,Xiaojun Zhou,Chuanglong He
In this study, an effective and facile strategy is reported to construct a multifunctional nanoplatform by in situ doping metal manganese on gold core mesoporous silica nanoparticles (Au@MMSN). After further modification of alendronate (Ald) on Au@MMSN, the obtained Au@MMSN-Ald efficiently integrates bone targeted chemo-chemodynamic combination therapy and dual-modality computed tomography/magnetic resonance (CT/MR) imaging into a single platform. In particular, Au@MMSN-Ald exhibits excellent tumor microenvironment responsive drug release efficiency. The doxorubicin hydrochloride (DOX) loaded Au@MMSN-Ald (DOX@Au@MMSN-Ald) is demonstrated with excellent targeted ability toward osteosarcoma. Accordingly, in a specific tumor microenvironment, DOX@Au@MMSN-Ald also displays outstanding combined efficiency for killing cancer cells in vitro and suppressing the osteosarcoma growth in vivo. Benefiting from the Au nanoparticles confined in the core and manganese ions released from the shell, CT and MR dual-modality imaging were performed to verify the effective accumulation of Au@MMSN-Ald at the tumor site. Overall, the constructed DOX@Au@MMSN-Ald nanoparticles integrated imaging guide, responsive drug release and combination therapy, which may provide some insight for further biomedical applications in efficient osteosarcoma therapy.
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