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
·
分子生物学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
DRUG RESISTANCE UPDATES
·
2024
·
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
·
药理学
·
分子生物学
·
转化医学
✓ 已验证
DOI
高影响因子
ONCOLOGY REPORTS
·
2020
·Vol. 44
·期 3
·927-938
·
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
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
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
·
药学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）