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: The SIRT1 expression in clinical pancreatic cancer samples were detected by immunohistochemistry (IHC). Compared to samples before chemotherapy, the results showed that the number of SIRT1-positive cells was significantly higher in pancreatic cancer samples after chemotherapy than those before chemotherapy (83.17 ± 5.42% vs 66.83 ± 6.01%, P < 0.05). Simultaneously, the IHC results also showed that SIRT1 did not only locate primarily to the nucleus but also had some minor cytoplasmic localization in pancreatic cancer cells (Fig. 9a). Furthermore, the SIRT1 expression was accurately evaluated by qRT-PCR and Western blot analysis. Compared to pancreatic cancer tissues before chemotherapy, the SIRT1 expression was clearly upregulated in pancreatic cancer after chemotherapy in mRNA (12.14 ± 6.68 vs 2.96 ± 2.06, P < 0.05) and protein levels (0.88 ± 0.41 vs 0.22 ± 0.10, P < 0.05) (Fig. 9b,c). The results roughly coincide with the IHC analysis.
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.