Succinate Dehydrogenase Subunit B Regulates Cisplatin Resistance via DNA Damage in Human Ovarian Cancer Cells

Background: Succinate dehydrogenase subunit B (SDHB) is one of succinate dehydrogenase subunits which is an important enzyme in the tricarboxylic acid (TCA) cycle. SDHB has been found expressed low in human ovarian carcinoma compared to human ovarian normal epithelium tissues. Previous studies have confirmed that the high expression of SDHB significantly inhibits the proliferation, invasion and migration of ovarian cancer cells, indicating that SDHB plays a role of tumor suppressor gene in ovarian cancer. But the role of SDHB in ovarian cancer chemotherapy is unknown. Methods: Using the SDHB specific siRNA and overexpression plasmid, the expression of SDHB was silenced and conversely overexpressed in ovarian cancer cell lines SKOV3 and A2780, respectively. The role of SDHB in ovarian cancer chemotherapy was investigated in vitro, using CCK8 and Colony formation assays. Immunohistochemistry was used to exam the expression of SDHB in human ovarian cancer cisplatin-resistant tissues and corresponding cisplatin-sensitive tissues. To explore the mechanism, DNA damage repair related proteins such as γ-H2AX and ERCC1were examined by western blot in SKOV3 and A2780 cells. Results: SDHB expressed lower in human ovarian cancer cisplatin-resistant tissues than the corresponding cisplatin-sensitive tissues. SDHB silencing increased drug resistance and SDHB overexpression showed the opposite results in SKOV3 and A2780 cells. In SDHB -silenced cancer cells, the level of ERCC1, which contributes to platinum drug resistance by promoting DNA repair, was increased, andγ-H2AX, which is related to cell apoptosis and drug resistance was decreased. Conclusions: In this research, we demonstrated SDHB silencing reduced chemosensitivity in SKOV3 and A2780 by improving the repair of DNA damage. These results suggested that SDHB might represent a potential therapeutic target to overcome chemosensitivity in human ovarian carcinoma.