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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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Sirtuin 1 (SIRT1) expression was evaluated in pancreatic cancer samples before and after chemotherapy. (a) SIRT1 expression in pancreatic cancer samples before chemotherapy (BC) and after chemotherapy (AC) (n = 8) was analyzed by immunohistochemical staining with an anti-SIRT1 antibody in paraffin-embedded tissue sections. (b) Representative expression of SIRT1 was analyzed in pancreatic cancer samples before (n = 4) and after chemotherapy (n = 4) by Western blot analysis. The β-actin level was assessed as a loading control. (c) Expression of SIRT1 was also detected in RNA levels by quantitative RT-PCR. Representative results are shown.
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fig09: Sirtuin 1 (SIRT1) expression was evaluated in pancreatic cancer samples before and after chemotherapy. (a) SIRT1 expression in pancreatic cancer samples before chemotherapy (BC) and after chemotherapy (AC) (n = 8) was analyzed by immunohistochemical staining with an anti-SIRT1 antibody in paraffin-embedded tissue sections. (b) Representative expression of SIRT1 was analyzed in pancreatic cancer samples before (n = 4) and after chemotherapy (n = 4) by Western blot analysis. The β-actin level was assessed as a loading control. (c) Expression of SIRT1 was also detected in RNA levels by quantitative RT-PCR. Representative results are shown.

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.


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)

Sirtuin 1 (SIRT1) expression was evaluated in pancreatic cancer samples before and after chemotherapy. (a) SIRT1 expression in pancreatic cancer samples before chemotherapy (BC) and after chemotherapy (AC) (n = 8) was analyzed by immunohistochemical staining with an anti-SIRT1 antibody in paraffin-embedded tissue sections. (b) Representative expression of SIRT1 was analyzed in pancreatic cancer samples before (n = 4) and after chemotherapy (n = 4) by Western blot analysis. The β-actin level was assessed as a loading control. (c) Expression of SIRT1 was also detected in RNA levels by quantitative RT-PCR. Representative results are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig09: Sirtuin 1 (SIRT1) expression was evaluated in pancreatic cancer samples before and after chemotherapy. (a) SIRT1 expression in pancreatic cancer samples before chemotherapy (BC) and after chemotherapy (AC) (n = 8) was analyzed by immunohistochemical staining with an anti-SIRT1 antibody in paraffin-embedded tissue sections. (b) Representative expression of SIRT1 was analyzed in pancreatic cancer samples before (n = 4) and after chemotherapy (n = 4) by Western blot analysis. The β-actin level was assessed as a loading control. (c) Expression of SIRT1 was also detected in RNA levels by quantitative RT-PCR. Representative results are shown.
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.

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