Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress.
Bottom Line: Moreover, the decrease in SIRT1 activity with special inhibitor EX527 had a synergic effect on chemotherapy with gemcitabine in PANC-1 and ASPC-1 cell lines, which significantly promoted apoptosis, senescence, and G0 /G1 cycle arrest.Western blot results also showed that SIRT1, acetylated-p53, FOXO3a, and p21 were upregulated after combined treatment, whereas no obvious change was evident in total p53 protein.Thus, our results indicated a special role for SIRT1 in the regulation of adaptive response to chemotherapy-induced stress, which is involved in chemoresistance.
Affiliation: Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China; Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Show MeSH
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Mentions: To assess the mechanism by which EX527 sensitized PANC-1 and ASPC-1 cells to GEM, apoptosis and the cell cycle were analyzed by FACS. As shown in Figure 5(a), compared with the PANC-1 control group (3.46 ± 0.71%), apoptosis was increased in PANC-1 cells treated with GEM (50 μg/mL, 4.81 ± 0.68%) or EX527 (2 μM, 6.06 ± 0.63%); the combination of GEM and EX527 treatment caused a significant increase in apoptosis (11.07 ± 0.90%, P < 0.01). Similar results were observed in ASPC-1 cells (Fig. 5b), which suggested that EX527 had synergic effects on induction of apoptosis with GEM in pancreatic cancer cells.
Affiliation: Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China; Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.