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Published on: August 2, 2024
[Improve the chemosensitivity of resistant ovarian cancer cell by small RNA interference]
Jiang-Yan Lou1, Zhi-Lan Peng, Ying Zheng
1Department of Obsterics and Gynecology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To investigate the effects of siRNA on the drug resistance reversal of ovarian cancer cell.
Methods:
The siRNA was transfected into human ovarian cancer cell line OVCAR8/TR by liposome. ATP-bioluminence assay was applied to measure the drug sensitivity to four chemotherapeutic agents before and after transfection.
Results:
ATP-bioluminence assay showed that OVCAR8/TR cells were resistant to cDDP, ADM and Taxol. After siRNA transfection, OVCAR8/TR cells were sensitive to ADM and Taxol which are tansported by P-gp. The inhibition rate of ADM was improved from 37% to 58%, and that of Taxol was improved from 26% to 78%. However, the resistance of OVCAR8/TR cells to cDDP was not reversed.
Conclusion:
siRNA can effectively improve the drug resistance to chemotherapeutic agents which are transfered by P-gp. The RNA interference can reverse MDR1-mediated drug resistance in ovarian cancer cell.
Insights
Small interfering RNA (siRNA) reversed multidrug resistance in ovarian cancer cells by enhancing sensitivity to P-glycoprotein-transported drugs. This RNA interference approach offers a potential strategy for overcoming chemotherapy resistance.
Area of Science:
- Molecular Biology
- Oncology
- Pharmacology
Background:
- Ovarian cancer often develops resistance to chemotherapy, limiting treatment efficacy.
- Multidrug resistance (MDR) is a significant challenge in ovarian cancer treatment, mediated by proteins like P-glycoprotein (P-gp).
Purpose of the Study:
- To evaluate the efficacy of small interfering RNA (siRNA) in reversing drug resistance in ovarian cancer cells.
- To investigate the impact of siRNA on the sensitivity of ovarian cancer cells to chemotherapeutic agents.
Main Methods:
- Human ovarian cancer cell line OVCAR8/TR was used.
- siRNA was delivered into cells using lipofection.
- ATP-bioluminescence assay measured drug sensitivity before and after siRNA transfection.
Main Results:
- OVCAR8/TR cells exhibited resistance to cisplatin (cDDP), doxorubicin (ADM), and paclitaxel (Taxol).
- Post-siRNA transfection, cells showed increased sensitivity to ADM and Taxol, drugs transported by P-gp.
- The inhibition rate for ADM increased from 37% to 58%, and for Taxol from 26% to 78%.
Conclusions:
- siRNA effectively reverses P-gp-mediated drug resistance in ovarian cancer.
- RNA interference is a promising strategy for overcoming MDR1-mediated drug resistance in ovarian cancer cells.
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