Frontiers in Oncology
·
2021
·
IF 6.244
Yang Feng,Zhao Ziyu,Cai Shaoyi,Ling Li,Hong Leying,Tao Liang,Wang Qin
Carboplatin resistance in ovarian cancer (OV) is a major medical problem. Thus, there is an urgent need to find novel therapeutic targets to improve the prognosis of patients with carboplatin-resistant OV. Accumulating evidence indicates that the gene COL1A1 (collagen type I alpha 1 chain) has an important role in chemoresistance and could be a therapeutic target. However, there have been no reports about the role of COL1A1 in carboplatin-resistant OV. This study aimed to establish the detailed molecular mechanism of COL1A1 and predict potential drugs for its treatment. We found that COL1A1 had a pivotal role in carboplatin resistance in OV by weighted gene correlation network analysis and survival analysis. Moreover, we constructed a competing endogenous RNA network (LINC00052/SMCR5-miR-98-COL1A1) based on multi-omics data and experiments to explore the upstream regulatory mechanisms of COL1A1. Two key pathways involving COL1A1 in carboplatin resistance were identified by co-expression analysis and pathway enrichment: the “ECM-receptor interaction” and “focal adhesion” Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, combining these results with those of cell viability assays, we proposed that ZINC000085537017 and quercetin were potential drugs for COL1A1 based on virtual screening and the TCMSP database, respectively. These results might help to improve the outcome of OV in the future.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2025
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IF 3.1
Liu Xiaozhen,Hao Jiao,Yuan Youyuan,Liu Fang
Recent findings have demonstrated that Docetaxel (DTX) and Carboplatin (CRP) exhibit significant anticancer and antiproliferative properties in cancer cells. This study aims to explore the effects of DTX on enhancing CRP-induced apoptosis in liver cancer cells and the associated molecular pathways. DTX and CRP cell viability against SMMC-7721 and Bel7402 cells by MTT test. The IC 50 values of CRP, DTX, and DTX + CRP for 35 μM, 4.69 μM, and 3.12 μM for SMMC-7721 cells, respectively. The outcomes of the respective fluorescence staining assays displayed that DTX + CRP remarkably enhanced the reactive oxygen species, diminished MMP, and triggered apoptosis in SMMC-7721 cells. DTX + CRP diminished the levels of GSH, CAT, and SOD while enhancing MDA contents in SMMC-7721 cell lines. In SMMC-7721 cells subjected to DTX + CRP, the Bax, Bcl-2, CyC, caspase-3, -8, and -9 expressions were fourfold increased, while Bcl-2 expression was threefold reduced. DTX + CRP enhanced the anticancer efficacy of human liver cancer cells by causing cellular oxidative stress. The hemocompatibility of DTX, CRP, and DTX + CRP was measured at different concentrations. Overall, the results indicate that these DTX + CRP possess potential biomedical uses due to their reduced hemotoxicity, cytotoxicity, and enhanced physiological milieu stability.
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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产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
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2025
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IF 2.7
Weibin Luo,Zhengyuan Yang,Shihua Gao,Bin Peng
Lung carcinoma is one of the most severe types of cancer, characterized by a dismal prognosis and low overall survival rate, primarily due to late diagnosis and the ineffectiveness of standard treatments. Hence, this study aimed to develop bevacizumab (BZ)-functionalized albumin (BS)-clad, carboplatin (CP)-loaded hollow mesoporous selenium (HMS) nanoparticles (BBHMSC) for the targeted administration of HER2+ Calu-3 lung cancer. The structural properties of these nanoparticles were characterized using transmission electron microscopy (TEM). Cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]- 2,5-diphenyltetrazolium bromide (MTT) assay. The images were obtained from fluorescence microscopy. The in vitro characterization of the pharmacological characteristics indicated that BBHMSC was uniformly disseminated, with a particle size of 171.52 ± 4.3 nm. In vitro release tests demonstrated that BBHMSC proficiently regulated the release of CP in the tumor microenvironment (elevated glutathione concentration), achieving a cumulative release rate of 87.1 ± 3.9% over 48 h. A cellular uptake assay validated that BBHMSC has an effective tumor-targeting capability. In vitro cell investigations, MTT studies, have shown that BBHMSC dramatically suppresses proliferation and growth. Further, BBHMSC enhances the apoptosis of HER2+ Calu-3 cells by fluorescence and flow cytometry methods. The data indicate that BBHMSC may be an effective targeted therapy for HER2+ti lung cancer.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
ONCOLOGY REPORTS
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2020
·Vol. 44
·期 3
·927-938
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IF 3.417
Songhui Zhou,Ruicheng Wang,Hong Xiao
The resistance of cancer cells to carboplatin restricts their efficacy in the clinical setting, and a solution to reverse the resistance is urgently required for the treatment of ovarian cancer. An increasing number of studies have found associations between obesity and the incidence, and mortality rates of female cancer. However, the association between adipocytes and the resistance of ovarian cancer has rarely been reported. Based on this, the present study first revealed the inductive effect of adipocytes on the resistance of ovarian cancer to carboplatin using in vivo and in vitro experiments. Subsequently, it was identified that the angiopoietin‑like 4 (ANGPTL4) secreted by adipocytes played a vital role in the resistance of ovarian cancer using bioinformatics analysis, cellular and molecular biological experiments, as well as forward and backward validation. The glycosylated ANGPTL4 protein could bind with integrin α5β1 on the surface of ovarian cancer cells; following which, it could activate the c‑myc/NF‑κB pathway and stimulate the expression of the antiapoptotic protein Bcl‑xL, as well as the ABC transporter family members ABCB1, ABCC1 and ABCG2. Thus, inducing the resistance of ovarian cancer to carboplatin. In conclusion, targeting the adipocyte‑derived ANGPTL4 combined with the application of carboplatin contributes to the clinical treatment for ovarian cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2025
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IF 2.5
Hetong Wang,Wei Wang,Qin Tang,Xun Liu,Limin Zhu,Di Sun,Tingting Lin
Milk exosomes have also been widely used as emerging delivery vehicles for various therapeutic cargoes. Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. However, the therapeutic efficacy is severely hampered by the presence of blood–retinal barrier (BRB) and systemic side effects. Legumain (LGMN) can be used as a target for tumor microenvironment responsive delivery design and therapeutic applications. Here, a LGMN-sensitive peptide KC26-modified milk exosomes loaded with carboplatin (CBP-KC26-MExos). The system enables milk exosomes loaded with carboplatin (CBP) to reach the target cells by binding to LGMN, improves tumor targeting, enhances cellular uptake and apoptosis, inhibits cell proliferation, invasion and migration. Intravenous injection of CBP-KC26-MExos cross the BRB significantly inhibited intraocular tumor progression and reduced CBP toxicity. We have developed a ‘drug-target-carrier’ approach and proposed an enzyme sensitive peptide (KC26) modified milk exosomes loaded with CBP, providing a perspective for exploring targeted therapy of tumor cells and tumor microenvironment, and offering a promising clinical strategy for the treatment of retinoblastoma.
研究领域:
肿瘤学
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药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cancer Management and Research
·
2020
·
IF 2.886
Jun Sha,Dandan Cao,Rui Cui,Lu Xia,Xin Hua,Yuan Lu,Shuhua Han
Introduction Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC). Materials and Methods First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI. Results In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest. Discussion Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma.
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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DOI
PubMed
高影响因子
Translational Cancer Research
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2021
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IF 1.241
Dong Luo,Wenzhi Chen,Wei Wang,Junlin Chen,Haopeng Xu,Jinyun Chen,Yan Wang
Background Our team has previously reported that low intensity pulsed ultrasound (LIPUS) can alleviate myelosuppression in rats induced by single chemotherapy drugs. But in clinics, chemotherapy is often performed with multiple drugs simultaneously. To be closer to the clinical status quo, this experiment was designed to show whether it was the same effect of LIPUS on myelosuppression caused by combination therapy of chemotherapy drugs. Methods The rat model of myelosuppression was established by continuous injection of paclitaxel and carboplatin for 4 days. These myelosuppressive rats were randomly divided into LIPUS group (n=40) and control group (n=40). The LIPUS group was given continuous LIPUS irradiation for 7 days, while the control group was given sham irradiation (no energy output). The evaluation of blood cells counts, Hematoxylin-Eosin staining (H&E staining), scanning electron microscopy, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qPCR) was then performed. Results The results showed in the LIPUS group the blood cells count, hematopoietic tissue of bone marrow, the colonies formed from adhering of bone marrow stromal cells, levels of hematopoietic regulators and adhesion molecules all increased (LIPUS group vs. control group, P<0.05). Conclusions The results indicated that LIPUS can relieve myelosuppression induced by combined treatment of paclitaxel and carboplatin. The mechanisms may be LIPUS can increase the levels of hematopoietic regulators and adhesion molecules.
研究领域:
肿瘤学
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药理学
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实验医学
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产品关联
DOI
PubMed
高影响因子
DRUG RESISTANCE UPDATES
·
2024
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IF 15.8
Feifeng Song,Xiaofen Yi,Xiaowei Zheng,Zhentao Zhang,Linqian Zhao,Yan Shen,Ye Zhi,Ting Liu,Xiaozhen Liu,Tong Xu,Xiaoping Hu,Yiwen Zhang,Huafeng Shou,Ping Huang
Aims Ovarian cancer (OC) remains a significant challenge in oncology due to high rates of drug resistance and disease relapse following standard treatment with surgery and platinum-based chemotherapy. Despite the widespread use of these treatments, no effective biomarkers currently exist to identify which patients will respond favorably to therapy. This study introduces a zebrafish patient-derived xenograft (PDX) system, capable of replicating both the carboplatin response and metastatic behavior observed in OC patients, within a rapid 3-day assay period. Methods Two OC cell lines: carboplatin-sensitive (A2780) and resistant (OVCAR8) were used to assess differential responses to treatment in murine and zebrafish xenograft models. Tumor tissues from 16 OC patients were implanted into zebrafish embryos to test carboplatin responses and predict metastasis. Additionally, eight clinical OC samples were directly implanted into zebrafish embryos as part of a proof-of-concept demonstration. Results The zebrafish xenografts accurately reflected the carboplatin sensitivity and resistance patterns seen in in vitro and murine models. The zebrafish PDX model demonstrated a 67 % success rate for implantation and a 100 % success rate for engraftment. Notably, the model effectively distinguished between metastatic and non-metastatic disease, with an area under the ROC curve (AUC) of 0.818. Furthermore, the zebrafish PDX model showed a high concordance with patient-specific responses to carboplatin. Conclusions This zebrafish PDX model offers a fast, accurate, and clinically relevant platform for evaluating carboplatin response and predicting metastasis in OC patients. It holds significant potential for advancing personalized medicine, allowing for more precise therapeutic outcome predictions and individualized treatment strategies.
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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转化医学
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DOI
高影响因子
Drug Design Development and Therapy
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2022
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IF 4.319
Junjian Wang
Purpose Cervical cancer is one of the most common causes of death among women globally. Combinations of cisplatin, paclitaxel, bevacizumab, carboplatin, topotecan, and gemcitabine are recommended as first-line therapies.Methods This study focuses on the development of folate-decorated, pH-sensitive lipid-polymer hybrid nanoparticles (LPNs). Loading carboplatin (CBP) and paclitaxel (PTX), LPNs were expected to combine the therapeutic effects of CBP and PTX, thus show synergistic ability on cervical cancer.Results FA-CBP/PTX-LPNs showed the sizes of 169.9 ± 5.6 nm, with a narrow size distribution of 0.151 ± 0.023. FA-CBP/PTX-LPNs exhibited pH-responsive drug release, high cellular uptake efficiency (66.7 ± 3.1%), and prominent cell inhibition capacity (23 ± 1.1%). In vivo tumor distribution and tumor inhibition efficiency of FA-CBP/PTX-LPNs was the highest, with no obvious body weight lost.Conclusion High tumor distribution and remarkable antitumor efficiency obtained using in vitro as well as in vivo models further proved the FA-CBP/PTX-LPNs is a promising tool for cervical cancer therapy.
研究领域:
肿瘤学
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药剂学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Xiumei Zhu,Yan Peng,Liyan Qiu
Carboplatin is one of the few platinum-based antitumor drugs used worldwide. Unfortunately, systemic carboplatin therapy is limited by its dose-related myelosuppression. In this study, a viable way to reduce the serious myelotoxicity of carboplatin while improving its therapeutic efficacy using amino-functionalized polyphosphazene vesicles is reported. First, three polyphosphazenes with different amino content were synthesized by amidating hydrophobic side groups; these polyphosphazenes could self-assemble into polymersomes with similar particle size and morphology. Based on FTIR analysis, hydrogen bonding interactions between the polymeric carriers and carboplatin were validated and shown to predominantly contribute to the significant improvement of drug loading in polymersomes. Therefore, it turned out that the amino level of polymers played a substantial role in carboplatin encapsulation. Then, PEAP-2-C polymersomes were optimized for further experimental verification to achieve depressed carboplatin-induced myelotoxicity as well as promote curative effects against CT-26 colon adenocarcinoma. These results in vitro and in vivo proved that amino-functionalized polyphosphazene vesicles have great potential for carboplatin delivery in the application of cancer therapy.
研究领域:
药学
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纳米技术
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2020
·Vol. 47
·期 6
·1083-1091
·
IF 2.456
Zhu Wang,Qianqian Wang,Tao He,Wen Li,Yan Liu,Yuan Fan,Yanping Wang,Qi Wang,Jie Chen
Carboplatin (CBP) is a widely used targeted anticancer therapeutic drug; however, multi-drug resistance induced by the accumulation of CBP eventually causes diseases progression. The anti-malarial drug artesunate (ART) also exerts anticancer effects in various cancers; however, the combined effect of ART and CBP on non-small cell lung cancer (NSCLC) remains unclear. In the present study, the NSCLC cell line A549 was pretreated with various concentrations of CBP, ART and gemcitabine (GEM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted to detect cell viability. Cell apoptosis was evaluated by both flow cytometry and TUNEL apoptotic assay. The expression profiles of cell cycle-related proteins and apoptotic proteins were determined by western blot. Cell clone numbers were visualized using crystal violet staining. Here, we found that both CBP and ART suppressed cell viability, and promoted cell apoptosis, and the combined application of ART and CBP at a lower concentration exhibited synergistic effects. Specifically, the combination of ART and CBP at a lower concentration suppressed cell clone numbers, promoted cell cycle arrest at the G 2 /M phase, and induced the expression of the cell cycle and apoptosis-related proteins BAX, p21, p53, and Caspase-3, while decreasing Bcl-2 and Cyclin B1 expression. Based on these results, we concluded that combined application of ART and CBP exerts synergistic anti-tumour effects on NSCLC by enhancing cell apoptosis in a mitochondria-dependent manner.
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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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Yang Bing,Liu Wenxu,Li Meiying,Mo Jingxin
Despite intensive research, ovarian cancer has the highest mortality rates among gynecological malignancies, partly because of its rapid acquisition of chemoresistance to platinum therapy. Hence, strategies are needed to effectively treat carboplatin-resistant ovarian cancer. In this study, we designed and prepared hyaluronic acid-decorated metal-organic frameworks for the targeted delivery of GSK-J1, a JMJD3 demethylase inhibitor (HA@MOF@GSK-J1) for the synergistic treatment of carboplatin-resistant ovarian cancer. HA@MOF@GSK-J1 showed outstanding effectiveness in the inhibition of ovarian cancer in vitro. Furthermore, HA@MOF@GSK-J1 demonstrated higher induction of apoptosis, reduced cell motility, and diminished cell spheroids by attenuating HER2 activity through the effectual activation of H3K27 methylation in its promoter area. Finally, our in vivo results confirmed that HA@MOF@GSK-J1 had better treatment efficacy for carboplatin-resistant ovarian tumor xenografts. Our results highlight the potential of HA@MOF@GSK-J1 as an effective strategy to improve the treatment of carboplatin-resistant ovarian cancer.
研究领域:
肿瘤学
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药学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
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