Suppresses Cell Proliferation and Apoptosis via Regulation of SIRT1/PGC-1α/NRF2 Axis in Pancreatic Cancer.

Objective: Our study aimed to investigate function and mechanism of in proliferation and apoptosis of pancreatic cancer (PC) cells by regulating NAD+-dependent histone deacetylase sirtulin 1 (SIRT1).

Materials And Methods: This experimental study included two PC cell lines AsPC-1 and PANC-1 in which expression levels of and were manipulated. The level of was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Expression levels of SIRT1, BCL-2, BAX, cleaved CASPASE-8/9/3, PARP, PGC-1α, NRF2, eNOS and iNOS were examined via RT-qPCR and western blotting, respectively. The binding sites of on the SIRT1 were examined via dual-luciferase assay. Cell proliferation and apoptosis were examined by MTT assay, colony formation assay, Annexin-V/PI staining and TUNEL assay. The oxidative metabolic changes were monitored by reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) detection.

Results: could specifically target the 3'-UTR of and reduce its expression in PC cells. Either elevated expression of or partial loss of SIRT1 inhibited cell proliferation and induced cell apoptosis. Accumulation of BAX and cleaved CASPASE-8/9/3, inhibition of PGC-1α/NRF2 pathway, increase oxidative stress and reduction of BCL-2 as well as uncleaved PARP were found in the presence of or the absence of . Overexpression of could reduce anti-proliferative and pro-apoptotic effects of .

Conclusion: Overall, this study concluded that -dependent inhibition displays anti-proliferative and proapoptotic roles in PC cells via PGC-1α/NRF2 pathway, which highlights as a potential target for PC treatment.