[The relationship between multi-drug resistance gene expression and drug resistance of ovarian carcinoma]
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1Peking Union Hospital, Peking Union Medical College Chinese Academy of Medical Science, Beijing.
Objective:
To study the relationship between multi-drug-resistance (MDR1) gene expression and the drug resistance of ovarian carcinoma and the reversing potency of drug-resistance modifying agent--cyclosporin A (CsA).
Methods:
Tumor-bearing mice of ovarian carcinoma cell (OVCA3) were divided randomly into three groups: control group, adriamycin (ADM) group and ADM +CsA group. The tumor growth rate and the survival rate of mice were investigated and compared among the groups. 32 frozen specimens of ovarian carcinoma tissue from patients were examined for the expression of MDR1 gene by means of RT-PCR.
Result:
Ovarian carcinoma cells with positive MDR1 gene expression showed cross drug-resistance to ADM, daunorubicin (DNR), vincristine (VCR) and etoposide (VP-16), the value of inhibiting concentration (IC50) is 4.1-15.5 times of that of the cells with negative MDR1 gene expression. To tumor-bearing mice, there was significant difference in tumor growth rate between mice given combined therapy of CsA + ADM and those given ADM only (P<0.01) Of the 32 frozen specimens of ovarian carcinoma tissue, there was no confirmed relationship between MDR1 gene expression and the pathologic type or differential grade. The possibility of poor prognosis of patients with positive MDR1, gene expression was 16.07 (1.78-144.7) times of that of patients with negative MDR1 gene expression.
Conclusion:
MDR-related drug can induce the overexpression of MDR1 gene and result in the appearance of the multidrug resistance phenomenon. CsA can partially reverse the multidrug resistance of ovarian carcinoma cells both in vitro and in vivo. Detection of MDR1 gene expression in patients of ovarian carcinoma could be used as an index to predict the prognosis of the patients.
Insights
Multi-drug resistance (MDR) in ovarian carcinoma is linked to MDR1 gene expression. Cyclosporin A (CsA) can partially reverse this resistance, and MDR1 detection may predict patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Ovarian carcinoma often develops resistance to chemotherapy.
- The multi-drug resistance (MDR) phenomenon is a significant challenge in cancer treatment.
- The MDR1 gene plays a crucial role in mediating drug resistance in various cancers.
Purpose:
- To investigate the correlation between MDR1 gene expression and drug resistance in ovarian carcinoma.
- To evaluate the efficacy of Cyclosporin A (CsA) in reversing MDR in ovarian carcinoma.
- To determine if MDR1 gene expression can serve as a prognostic marker for ovarian cancer patients.
Summary:
- Ovarian carcinoma cells with positive MDR1 gene expression exhibited cross-resistance to multiple chemotherapy drugs (ADM, DNR, VCR, VP-16).
- In vivo studies showed that combined therapy with CsA and ADM significantly reduced tumor growth compared to ADM alone in mice.
- MDR1 gene expression was not correlated with pathological type or grade but was associated with a significantly higher risk of poor prognosis.
Impact:
- MDR1 gene overexpression is implicated in the development of multi-drug resistance in ovarian carcinoma.
- Cyclosporin A demonstrates potential in overcoming chemoresistance in ovarian cancer, both in vitro and in vivo.
- MDR1 gene expression analysis offers a valuable tool for predicting patient outcomes in ovarian carcinoma, guiding personalized treatment strategies.
