Clinical relevance of Vav3.1 expression in ovarian cancer and involvement in mechanisms causing genuine multi-drug resistance.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e17528-e17528
Author(s):  
Daniel Uwe Reimer ◽  
Maximilian Boesch ◽  
Sieghart Sopper ◽  
Dominik Georg Friedrich Wolf ◽  
Anouk Gaber-Wagener ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Clinical Relevance ◽  
Multi Drug Resistance

scholarly journals Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cell Lines Responds Differently to Cell Culture Dimensionality

2020 ◽  
Author(s):  
Vasilij Koshkin ◽  
Mariana Bleker de Oliveira ◽  
Chun Peng ◽  
Laurie Aiiles ◽  
Geoffrey Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Rate Constant ◽  
Cell Number ◽  
Reaction Rate Constant ◽  
Multi Drug Resistance ◽  
Cell Clustering ◽  
Ovarian Cancer Cell Lines ◽  
Efflux Rate Constant ◽  
Drug Naïve

Does cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.

scholarly journals Heat Shock Protein 90 Triggers Multi-Drug Resistance of Ovarian Cancer via AKT/GSK3β/β-Catenin Signaling

2021 ◽  
Vol 11 ◽  
Author(s):  
Lan Yin ◽  
Yuhan Yang ◽  
Wanglong Zhu ◽  
Yu Xian ◽  
Zhengyu Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Heat Shock ◽  
Cancer Cells ◽  
Transcriptional Activity ◽  
Heat Shock Protein 90 ◽  
Multi Drug Resistance ◽  
Ovarian Cancer Cells ◽  
Drug Resistant ◽  
Resistance Protein

Ovarian cancer is the most lethal gynaecologic tumor, with which multi-drug resistance as the major therapeutic hindrance. Heat shock protein 90 (Hsp90) has been involved in cancer malignant behaviors. However, its role and mechanism in multi-drug resistance of ovarian cancer remains poorly understood. Our results demonstrated that Hsp90 was overexpressed in multi-drug resistant ovarian cancer cells. Hsp90 downregulation by shHsp90 or inhibitor BIIB021 increased the sensitivity of multi-drug resistant ovarian cancer cells to paclitaxel and cisplatin, and augmented the drugs-induced apoptosis. Hsp90 positively regulated the expressions of multi-drug resistance protein 1 (P-gp/MDR1), breast cancer resistance protein (BCRP), Survivin and Bcl-2 expressions closely associated with multi-drug resistance. Moreover, overexpression of Hsp90 promoted β-catenin accumulation, while Hsp90 downregulation decreased the accumulation, nuclear translocation and transcriptional activity of β-catenin. We also identified that β-catenin was responsible for Hsp90-mediated expressions of P-gp, BCRP, Survivin, and Bcl-2. Furthermore, Hsp90 enhanced the AKT/GSK3β signaling, and AKT signaling played a critical role in Hsp90-induced accumulation and transcriptional activity of β-catenin, as well as multi-drug resistance to paclitaxel and cisplatin. In conclusion, Hsp90 enhanced the AKT/GSK3β/β-catenin signaling to induce multi-drug resistance of ovarian cancer. Suppressing Hsp90 chemosensitized multi-drug resistant ovarian cancer cells via impairing the AKT/GSK3β/β-catenin signaling, providing a promising therapeutic strategy for a successful treatment of ovarian cancer.

scholarly journals Multi-Drug-Resistance in Drug-Naive and Drug-Exposed Ovarian Cancer Cell Lines Responds Differently to Cell Culture Dimensionality

2020 ◽  
Author(s):  
Vasilij Koshkin ◽  
Mariana Bleker de Oliveira ◽  
Chun Peng ◽  
Laurie E. Ailles ◽  
Geoffrey Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Rate Constant ◽  
Cell Number ◽  
Reaction Rate Constant ◽  
Multi Drug Resistance ◽  
Cell Clustering ◽  
Ovarian Cancer Cell Lines ◽  
Efflux Rate Constant ◽  
Drug Naïve

AbstractDoes cell clustering influence intrinsic and acquired multi-drug resistance (MDR) differently? To address this question, we studied cultured monolayers (representing individual cells) and cultured spheroids (representing clusters) formed by drug-naïve (intrinsic MDR) and drug-exposed (acquired MDR) lines of ovarian cancer A2780 cells by cytometry of reaction rate constant (CRRC). MDR efflux was characterized by accurate and robust “cell number vs. MDR efflux rate constant (kMDR)” histograms. Both drug-naïve and drug-exposed monolayer cells presented unimodal histograms; the histogram of drug-exposed cells was shifted towards higher kMDR value suggesting greater MDR activity. Spheroids of drug-naïve cells presented a bimodal histogram indicating the presence of two subpopulations with different MDR activity. In contrast, spheroids of drug-exposed cells presented a unimodal histogram qualitatively similar to that of the monolayers of drug-exposed cells but with a moderate shift towards greater MDR activity. The observed greater effect of cell clustering on intrinsic than on acquired MDR can help guide the development of new therapeutic strategies targeting clusters of circulating tumor cells.

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