SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells

• Published in: Translational oncology 2017-08, Vol.10 (4), p.621-631
• Main Authors: Mvunta, David Hamisi, Miyamoto, Tsutomu, Asaka, Ryoichi, Yamada, Yasushi, Ando, Hirofumi, Higuchi, Shotaro, Ida, Koichi, Kashima, Hiroyasu, Shiozawa, Tanri
• Format: Article
• Language: English
• ISSN: 1936-5233; 1944-7124
• DOI: 10.1016/j.tranon.2017.05.005

BACKGROUND: SIRT1 is a longevity gene that forestalls aging and age-related diseases including cancer, and has recently attracted widespread attention due to its overexpression in some cancers. We previously identified the overexpression of SIRT1 in ovarian carcinoma (OvCa) as a poor prognostic factor. However, mechanistic insights into the function of SIRT1 in OvCa have yet to be elucidated. METHODS: Quantitative real-time reverse PCR (qRT-PCR) and Western blotting were employed to examine the expression of SIRT1 in a panel of human OvCa cell lines. si-RNA or sh-RNA and cDNA technologies were utilized to knockdown or overexpress SIRT1, respectively. The effects of SIRT1 on proliferation and chemoresistance were examined using a WST-1 assay, and the underlying mechanisms were confirmed using an apoptotic assay, and the quantification of glutathione (GSH), and reactive oxygen species (ROS). The aggressiveness of SIRT1 was analyzed using in vitro invasion and migration assays. RESULTS: SIRT1 was more strongly expressed in OvCa cell lines than in the immortalized ovarian epithelium at the gene and protein levels. Stress up-regulated the expression of SIRT1 in dose- and time-dependent manners. SIRT1 significantly enhanced the proliferation (P