Expression of Genes Related to Multidrug Resistance and Apoptosis in Human Ovarian Cancer Cell Lines, Sensitive and Resistant to Cisplatin / 대한산부인과학회잡지

ABSTRACT

OBJECTIVE: The resistance mechanisms of tumor cells to chemotherapeutic drugs are known as the followings; the alterations in the drug transport and activation, the enhanced expression of the DNA repair and replication and the decreased apoptosis. The aim of this study is to examine a relative difference on the level of the mRNA expression of the multidrug resistance (MDR)-related and the apoptosis-associated genes between cisplastin-sensitive and cisplatin-resistant human ovarian cancer cell line. METHODS: MDR-associated genes (lrp, mdr1/p-glycoprotein, mrp) and PKC isozymes (alpha, beta1, beta2, epsilon, eta, theta), DNA mismatch repair (MMR) genes (hMLH1, hMSH2, hMSH3, hMSH6), DNA topology-related genes (topoisomerase IIalpha and beta) and apoptosis-related genes (p53, p21, mdm2, fas (Apo-1), trail (Apo-2L) were analyzed in cisplatin-sensitive ovarian cancer cell line A2780 and -resistant cell line A2780cp by complementary DNA polymerase chain reaction. RESULTS: The mdr1 and PKC eta in mRNA level were expressed in A2780cp, but not in A2780. The mRNA expressions of lrp, p21 and mdm2 were more increased in A2780cp than drug sensitive variant A2780, but not significantly correlated. In contrast mRNA expression of hMLH1, a kind of DNA MMR gene, was remarkably decreased and mRNA expression of hMSH2 was slightly decrease in A2780cp. However, the levels of mrp, topo II alpha and beta, hMSH3, hMSH6, p53, fas and trail were not affected. CONCLUSION: These results showed that mdr1/p-gp expression may be an important determinant of MDR phenotype in resistant cell line to chemotherapeutic agents, and PKC isozymes and DNA MMR genes may be responsible for cisplatin resistant in ovarian cancer.