| Expression analysis of genes related to multidrug resistance (MDR) in ovarian cancer cell line A2780 and cisplatinum resistant cell line A2780cp. |
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Jai Kyu Lee, Young Jeong Na, Young Mi Lee, Sung Yeoul Chang, Young Jin Moon, Sam Hyun Cho, Kyung Tai Kim, Youn Yeung Hwang |
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Department of Obstetrics and Gynecology, Laboratory for Clinical Investigation, College of Medicine, Hanyang University, Seoul, Korea. |
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| Abstract |
OBJECTIVE
Expressions of P-glycoprotein, the multidrug resistance-associated protein (MRP) and the lung resistance protein (LRP) with the MDR phenotype widely divergent in human cancer cell lines. This study focused on the altered gene expression related drug transport. METHODS: To examine correlations between MDR-associated genes and PKC isozyme with cisplatin resistance on the level of the mRNA expression, we analyzed MDR-associated gene (LRP, MDR1/P-gp and MRP) expression and PKC isozyme, topoisomerase II alpha and beta in cisplatin-sensitive ovarian cancer cell line A2780 and cisplatin - resistant cell line A2780cp using cDNA-PCR approach. RESULTS: LRP mRNA levels were significantly increased in A2780cp compared to the drug sensitive variant. In contrast, MRP mRNA levels were not significantly correlated with drug sensitivity. A modest increase in PKC(eta) and MDR1/P-gp mRNA expression activity was also observed in ovarian cancer A2780cp cell lines that were resistant to CDDP. The level of topoisomerase II alpha and beta were not affected. CONCLUSION: These results showed that MDR1/P-gp expression may be an important determinant of the MDR phenotype in cell lines intrinsically resistant to cancer chemotherapeutic agents and a multifactorial emergence of MDR phenotype of tumor with a possible involvement of the PKC isozymes may be associated with CDDP resistant ovarian cancer cell line. |
| Key Words:
Genes, MDR, Ovarian neoplasm, Reverse transcriptase polymerase chain reaction |
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