Objective.To investigate the relationship between mdrl gene expression and multidrug-resistance in o- varian carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug...Objective.To investigate the relationship between mdrl gene expression and multidrug-resistance in o- varian carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug sensitivity of OC/mdr-cell and OC/mdr+ cell in vitro, investigated the effect of cyclosporin A on reversing the multidrug resistance both in vitro and in the tumor-bearing mice model,detected the mdrl gene expre- sion in human ovarian carcinoma specimens. Main outcome measures. Anticancer drug sensitivity of both OC/mdr-cell and OC/mdr+ cell is mea- sured by the methods of MTT assays. mdrl gene expression is detected by the methods of RT-PCR. Results. Using MTT assay,OC/mdr+ cell is 4. 1 - 15. 5 times more resistant to VP-16,VCR,DNR, and DOX than OC/mdr-cell in vitro.2 μg/ml cyclosporine A(CsA)reduced the resistance of OC/mdr+ cell to DOX,from 0. 324±0. 072μg/ml to 0. 088±0. 024μg/ml. To OC/mdr－cell,CsA did not significantly in－ crease its sensitivity to DOX．Tumor-bearing mice with positive mdrl gene expression showed non-respon- siveness to DOX chemotherapy. When combined with intraperitoneal injection of CsA, the growth rate of tumor cells decreased significantly (P<0. 01 ). Only 4 of 23(17. 39% )tumors from patients who had not received chemotherapy exhibited positive mdrl gene expreession, while 6 of 9 (66. 67%)treated patients showed positive mdrl gene expression (Fisher exact test: P<0. 05 ). After cytoreductive surgery and chemotherapy, 14 of 19 untreated patients with negative mdrl gene expression had partial or complete re- sponse, while in patients with positive mdrl gene expression, 8 of 10 showed poor prognosis(Fisher exact test: P<0. 05 ). Conclusion. The expression of mdrl gene is associated with previous chemotherapy. CsA can reverse the resistance of mdr+ cells to indr-associated drs both in vitro and in vivo’ For the patients with ovarian carcinoma., the percentage of nonresponsiveness to the chemotherapy was found to be significantly higher among patients with positive mdrl gene expression than those with negative mdrl gene expression. mdrl gene expression can be detected to predict the clinical prognosis of patients with ovarian carcinoma.展开更多
文摘Objective.To investigate the relationship between mdrl gene expression and multidrug-resistance in o- varian carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug sensitivity of OC/mdr-cell and OC/mdr+ cell in vitro, investigated the effect of cyclosporin A on reversing the multidrug resistance both in vitro and in the tumor-bearing mice model,detected the mdrl gene expre- sion in human ovarian carcinoma specimens. Main outcome measures. Anticancer drug sensitivity of both OC/mdr-cell and OC/mdr+ cell is mea- sured by the methods of MTT assays. mdrl gene expression is detected by the methods of RT-PCR. Results. Using MTT assay,OC/mdr+ cell is 4. 1 - 15. 5 times more resistant to VP-16,VCR,DNR, and DOX than OC/mdr-cell in vitro.2 μg/ml cyclosporine A(CsA)reduced the resistance of OC/mdr+ cell to DOX,from 0. 324±0. 072μg/ml to 0. 088±0. 024μg/ml. To OC/mdr－cell,CsA did not significantly in－ crease its sensitivity to DOX．Tumor-bearing mice with positive mdrl gene expression showed non-respon- siveness to DOX chemotherapy. When combined with intraperitoneal injection of CsA, the growth rate of tumor cells decreased significantly (P<0. 01 ). Only 4 of 23(17. 39% )tumors from patients who had not received chemotherapy exhibited positive mdrl gene expreession, while 6 of 9 (66. 67%)treated patients showed positive mdrl gene expression (Fisher exact test: P<0. 05 ). After cytoreductive surgery and chemotherapy, 14 of 19 untreated patients with negative mdrl gene expression had partial or complete re- sponse, while in patients with positive mdrl gene expression, 8 of 10 showed poor prognosis(Fisher exact test: P<0. 05 ). Conclusion. The expression of mdrl gene is associated with previous chemotherapy. CsA can reverse the resistance of mdr+ cells to indr-associated drs both in vitro and in vivo’ For the patients with ovarian carcinoma., the percentage of nonresponsiveness to the chemotherapy was found to be significantly higher among patients with positive mdrl gene expression than those with negative mdrl gene expression. mdrl gene expression can be detected to predict the clinical prognosis of patients with ovarian carcinoma.
