Inhibition of SIRT1 combined with gemcitabine therapy for pancreatic carcinoma

Abstract

Background

Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods.

Methods

Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells) received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo.

Results

The cleaved poly ADP ribose polymerase (PARP)-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05) and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05).

Conclusion

Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single gemcitabine therapy. The combination therapy method is a potential treatment method for pancreatic carcinoma.

Keywords:

• pancreatic carcinoma
• combination therapy
• inhibition of SIRT1-gemcitabine

View correction statement:

The safety and efficacy of aspirin intake in photoselective vaporization laser treatment of benign prostate hyperplasia [Corrigendum]

Acknowledgments

The study was supported by grants from the Foundation of the Health Department of Zhejiang Province, People’s Republic of China (No 2010SSA008), the Foundation of Science and Technology Department of Jinhua (No 2010-3-003) and National Natural Science Foundation (No 81071960).

Disclosure

The authors report no conflicts of interest in this work.