MULTICELLULAR-MEDIATED RESISTANCE TO CISPLATIN AND TAXOL IN HUMAN OVARIAN CANCER SK-OV-3IP1 MULTICELLULAR AGGREGATES

作     者：陈建利 丰有吉 张琴 

作者机构：Department of Obstetrics and Gynecology Affiliated Hospital of Obstetrics and Gynecology Fudan University Shanghai 200011 Family Planning Service Station Laiwu Shangdong Province 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2002年第14卷第3期

页      面：165-169页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported by the National Natural Science Foundation of China (No. 30000177) 

主　　题：Multicellular aggregates Ovarian neoplasms Drug resistance 

摘      要：Objective: To investigate the chemosensitivity of ovarian cancer SK-OV-3ip1 multicellular aggregates (MCA) to cisplatin and taxol and to explore the possible mechanisms. Methods: Liquid overlay system was employed to obtain MCA. We detected the resistance using trypan blue exclusion testing, clonogenic assay, cell cycle profiles and apoptosis with flow cytometry (FCM). Results: After cisplatin exposure, MCA cells showed nearly equal cell viability with monolayer cells (P=0.05). After 40μM cisplatin exposure for 12 h, no clone (≥50 cells) was formed, but more viable cells attached to the bottom of 24-well plate in MCA group than monolayer. Furthermore, apoptosis rate and cell cycle profiles with FCM had no significant change between MCA and monolayer cells. After taxol exposure, however, trypan blue exclusion testing demonstrated higher cell viability in MCA cells (P=0.003) and higher clone formation rate in 100-cell group than monolayer cells (0.01P0.025). No significant difference was found in 50-cell or 200-cell group but more viable cells in MCA group were observed. Taxol exposure caused significantly decreased apoptosis rate in MCA cells than monolayer cells (P=0.012). Taxol induced significant cell arrest at G2-M phase in monolayer cells (P=0.001), but abrogation of G2-M arrest was observed in MCA cells (P=0.002). Conclusion: Compared with monolayer cells, MCA cells from the same SK-OV-3ip1 cell line appear to be more resistant to taxol but not to cisplatin. Cell cycle redistribution and multicellular-mediated inhibition of apoptosis can partially account for the resistance.