The Effect of the MDM2-p53 Loop on the Sensitivity of Ovarian Cancer Cells to Cisplatin

查看全文 作　　者：Zhi [1]Guo;Hong [1]Ni;Bin [2]Li;Wenge [1]Xing;Fang [1]Liu;Haipeng [1]Yu;Baoguo [1]Li;Xiuying [1]Guo

机构地区：[1]Department of Interventional Radiology, TianJin Medical University Cancer Hospital, Tianjin 300060, China.;[2]Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

出　　处：《Chinese Journal of Clinical Oncology》索引2006年第3卷第2期,共5页

摘　　要：OBJECTIVE To explore whether MDM2 transfection can alter the MDM2-p53 autoregulatory feedback loop so as to change the sensitivity of ovarian cancer cell lines to cisplatin. METHODS The ovarian cancer cell line A2780 expressing wild-type P53 and the ovarian cancer cell line SKOV-3 with the p53 null type were stably transfected with pCMV-MDM2 or pCMV as a control. The blocked expression of P53 was determined by Western blots. Cytotoxicity was assessed using the MTT assay and the trypan blue exclusion assay. Flow cytometry was used to detect changes in the cell cycle and removal of platinum -DNA adducts was measured by atomic absorption spec-troscopy. RESULTS (1) Parental A2780 and A2780-V cells (IC50= 15.14±1.39 μmol) have similar cisplatin sensitivities, whereas sensitivity to cisplatin in A2780-M cells (IC50=7.98±1.32 μmol) was 2 to 3 fold greater (P=0.001). The trypan blue exclusion assay demonstrated that cisplatin killed a higher percentage of A2780-M cells compared to A2780-V cells. There was no significant change following MDM2 transfection in SKOV-3 cells. (2) After cisplatin treatment, A2780-M cells showed a pronounced S-phase arrest, however, A2780 cells with the intact wild-type P53, arrested primarily at the G2/M transition. (3) Platinum uptake was similar for all of the A2780 cell lines after ciaplatin treatment, but the removal of plat-inum-DNA adducts was reduced in the A2780-M cells compared with A2780-V cells. CONCLUSION MDM2 increases cisplatin cytotoxicity in ovarian cancer cells by blocking the expression of p53 through the MDM2-p53 autoregulatory feedback loop. 关键词：MDM2-P53 卵巢癌肿瘤细胞顺铂

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The Effect of the MDM2-p53 Loop on the Sensitivity of Ovarian Cancer Cells to Cisplatin

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