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Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress.

Zhang JG, Hong DF, Zhang CW, Sun XD, Wang ZF, Shi Y, Liu JW, Shen GL, Zhang YB, Cheng J, Wang CY, Zhao G - Cancer Sci. (2014)

Bottom Line: In the present study, SIRT1 in PANC-1, BXPC-3, and ASPC-1 cells was upregulated after treatment with gemcitabine.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.

View Article: PubMed Central - PubMed

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.

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Chemosensitivity was induced in pancreatic cancer cells by EX527, through specifically deregulating the activity of sirtuin 1 (SIRT1). Downregulation of endogenous SIRT1 using RNA interference following EX527 (2 μM) treatment in PANC-1 (a) and ASPC-1 cells (b). The SIRT1 expression of siRNA plus EX527 treatment was also measured by Western blot analysis. All data are presented as means ± SD of three independent experiments. *P < 0.05 versus control group. NC, negative control.
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fig04: Chemosensitivity was induced in pancreatic cancer cells by EX527, through specifically deregulating the activity of sirtuin 1 (SIRT1). Downregulation of endogenous SIRT1 using RNA interference following EX527 (2 μM) treatment in PANC-1 (a) and ASPC-1 cells (b). The SIRT1 expression of siRNA plus EX527 treatment was also measured by Western blot analysis. All data are presented as means ± SD of three independent experiments. *P < 0.05 versus control group. NC, negative control.

Mentions: To further verify that the effect of EX527 on the chemosensitivity of pancreatic cancer cell lines is mainly due to inhibition of the SIRT1 pathway, EX527 and chemotherapy drugs were used to treated cell lines in which SIRT1 expression was deregulated by SIRT1 siRNA. Compared to control cells, the IC50 value of GEM was remarkably decreased in SIRT1-RNAi-PANC-1 cells (52.66 ± 2.65 vs 8.99 ± 3.02 μg/mL, P < 0.01) and SIRT1-RNAi-ASPC-1 cells (20.20 ± 1.98 vs 4.55 ± 2.29 μg/mL, P < 0.01). There was no further inhibition apparent in EX527-treated SIRT1-RNAi-PANC-1 and SIRT1-RNAi-ASPC-1 cells (IC50, 7.16 ± 2.92 and 3.57 ± 1.42 μg/mL, respectively, Fig. 4a). Furthermore, the Western blot results showed that EX527 had not further deregulated the SIRT1 expression in SIRT-RNAi transfected cells (Fig. 4b). These results revealed that the enhanced chemosensitivity of EX527 was critically through inhibiting SIRT1 activity.


Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress.

Zhang JG, Hong DF, Zhang CW, Sun XD, Wang ZF, Shi Y, Liu JW, Shen GL, Zhang YB, Cheng J, Wang CY, Zhao G - Cancer Sci. (2014)

Chemosensitivity was induced in pancreatic cancer cells by EX527, through specifically deregulating the activity of sirtuin 1 (SIRT1). Downregulation of endogenous SIRT1 using RNA interference following EX527 (2 μM) treatment in PANC-1 (a) and ASPC-1 cells (b). The SIRT1 expression of siRNA plus EX527 treatment was also measured by Western blot analysis. All data are presented as means ± SD of three independent experiments. *P < 0.05 versus control group. NC, negative control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317803&req=5

fig04: Chemosensitivity was induced in pancreatic cancer cells by EX527, through specifically deregulating the activity of sirtuin 1 (SIRT1). Downregulation of endogenous SIRT1 using RNA interference following EX527 (2 μM) treatment in PANC-1 (a) and ASPC-1 cells (b). The SIRT1 expression of siRNA plus EX527 treatment was also measured by Western blot analysis. All data are presented as means ± SD of three independent experiments. *P < 0.05 versus control group. NC, negative control.
Mentions: To further verify that the effect of EX527 on the chemosensitivity of pancreatic cancer cell lines is mainly due to inhibition of the SIRT1 pathway, EX527 and chemotherapy drugs were used to treated cell lines in which SIRT1 expression was deregulated by SIRT1 siRNA. Compared to control cells, the IC50 value of GEM was remarkably decreased in SIRT1-RNAi-PANC-1 cells (52.66 ± 2.65 vs 8.99 ± 3.02 μg/mL, P < 0.01) and SIRT1-RNAi-ASPC-1 cells (20.20 ± 1.98 vs 4.55 ± 2.29 μg/mL, P < 0.01). There was no further inhibition apparent in EX527-treated SIRT1-RNAi-PANC-1 and SIRT1-RNAi-ASPC-1 cells (IC50, 7.16 ± 2.92 and 3.57 ± 1.42 μg/mL, respectively, Fig. 4a). Furthermore, the Western blot results showed that EX527 had not further deregulated the SIRT1 expression in SIRT-RNAi transfected cells (Fig. 4b). These results revealed that the enhanced chemosensitivity of EX527 was critically through inhibiting SIRT1 activity.

Bottom Line: In the present study, SIRT1 in PANC-1, BXPC-3, and ASPC-1 cells was upregulated after treatment with gemcitabine.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.

View Article: PubMed Central - PubMed

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
Related in: MedlinePlus