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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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Effect of EX527 and (or) gemcitabine (GEM) on apoptosis of pancreatic cancer cells. PANC-1 (a) and ASPC-1 (b) cells were incubated with EX527 (2 μM) and (or) GEM (50 μg/mL) for 48 h. Cell apoptosis was monitored by annexin V staining and flow cytometry. The right lower quadrant of each plot represents early apoptotic cells and the right upper quadrant represents late apoptotic cells. The experiments were repeated twice with similar results. *P < 0.05, **P < 0.01 versus control group; #P < 0.01 versus single drug treatment.
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fig05: Effect of EX527 and (or) gemcitabine (GEM) on apoptosis of pancreatic cancer cells. PANC-1 (a) and ASPC-1 (b) cells were incubated with EX527 (2 μM) and (or) GEM (50 μg/mL) for 48 h. Cell apoptosis was monitored by annexin V staining and flow cytometry. The right lower quadrant of each plot represents early apoptotic cells and the right upper quadrant represents late apoptotic cells. The experiments were repeated twice with similar results. *P < 0.05, **P < 0.01 versus control group; #P < 0.01 versus single drug treatment.

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.


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)

Effect of EX527 and (or) gemcitabine (GEM) on apoptosis of pancreatic cancer cells. PANC-1 (a) and ASPC-1 (b) cells were incubated with EX527 (2 μM) and (or) GEM (50 μg/mL) for 48 h. Cell apoptosis was monitored by annexin V staining and flow cytometry. The right lower quadrant of each plot represents early apoptotic cells and the right upper quadrant represents late apoptotic cells. The experiments were repeated twice with similar results. *P < 0.05, **P < 0.01 versus control group; #P < 0.01 versus single drug treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Effect of EX527 and (or) gemcitabine (GEM) on apoptosis of pancreatic cancer cells. PANC-1 (a) and ASPC-1 (b) cells were incubated with EX527 (2 μM) and (or) GEM (50 μg/mL) for 48 h. Cell apoptosis was monitored by annexin V staining and flow cytometry. The right lower quadrant of each plot represents early apoptotic cells and the right upper quadrant represents late apoptotic cells. The experiments were repeated twice with similar results. *P < 0.05, **P < 0.01 versus control group; #P < 0.01 versus single drug treatment.
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.

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