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báo cáo hóa học:" Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells"

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học quốc tế đề tài : Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells | Rough et al. Journal of Ovarian Research 2010 3 13 http www.ovarianresearch.eom content 3 1 13 RESEARCH JOURNAL OF OVARIAN RESEARCH Open Access Anlti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells James J Rough 1 M Alexandra Monroy 1 2 Smitha Yerrum1 and John M Daly1 Abstract Background Ovarian cancer is the most common cause of cancer related death from gynecologic tumors in the United States. The insidious nature of the disease precludes early diagnosis therefore surgical debulking and chemotherapy are considered as standard treatment modalities for advanced stages. We investigated the effect of the LXR agonist T0901317 on ovarian cancer cell proliferation and apoptosis as a potential therapeutic agent. Results T0901317 treatment resulted in a significant P 0.001 inhibition of cell proliferation in a time- and dosedependent manner in CaOV3 SKOV3 and A2780 cells. Western blot analysis demonstrated an induction of p21 and p27 with a concominant reduction in phospho-RB protein levels. Cell cycle analysis demonstrated a significant P 0.001 arrest in the G1 cell cycle phase. Significant induction of Caspase-3 and BAX gene expression occurred with treatment. Induction of apoptosis was confirmed by significant P 0.001 elevation of caspase activity on FACS analysis caspase-glo assay BAX protein induction and decreased caspase 3 precursor protein expression on Western blot analysis. LXR a p knockdown experiments did not reverse the anti-proliferative and cytotoxic effects of T0901317. Conclusions The LXR agonist T0901317 significantly suppresses cell proliferation and induces programmed cell death in a dose- and time-dependent manner. Our results indicate that T0901317 induces its anti-proliferative and cytotoxic effects via an LXR-independent mechanism. Background Ovarian cancer is the most common cause of cancer related death from gynecologic tumors and the fourth leading cause of death due to cancer in women 1 2 . The insidious nature of the .