Anti-tumor activity of histone deacetylase inhibitors and the effect on ATP-binding cassette in ovarian carcinoma cells

作者：Chao K C^*; Chang C C; Yen M S; Wang P H

来源：European Journal of Gynaecological Oncology, 2010, 31(4): 402-410.

• Histone deacetylase inhibitors
• Multidrug-resistant protein
• Multidrug resistance-associated proteins
• Ovarian cancer cell line

Introduction: Ovarian cancer is of worldwide importance, and has a significantly high mortality rate due to therapy failure. Drug resistance might be one of most importance factors. Histone deacetylase inhibitors (HDACi) have been reported to be a new class of promising anti-tumor agents, thus this study aimed to investigate the effect of HDAC on the chemo-resistance genes of human ovarian carcinoma cell lines. Methods: The expressions of ATP binding cassette (ABC) transporter genes, multidrug-resistant protein (MDR1) and multidrug resistance-associated proteins (MRP1 and 2) of ovarian cancer cell lines OC-109 and SK-OV-3 after HDACi treatment were determined. Results: HDACi, including sodium butyrate (NaB), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) reduced ovarian cancer cell viability from 4.4% to 68.8%, in both dose- and time-dependent manners. The effect of HDACi on MDR1, MRP1, and MRP2 showed induced expression of MDR1 mRNA, but reduced mRNA expression of MRP1 and MRP2. Conclusions: The effect of HDACi on the reduced viability of ovarian cancer cell lines, concomitant with the induced expression of MDR1 and reduced expression of MRP1 and 2, might provide additional benefits in the management of ovarian cancers in the future.

• 出版日期2010