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Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China
Department of Nephrology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China
Department of Pharmacology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 7 November 2012; in revised form: 2 December 2012 / Accepted: 12 December 2012 / Published: 21 December 2012
Abstract: Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells.
Keywords: pancreatic carcinoma; rapamycin; mTOR; anti-tumor; apoptosis; autophagy
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MDPI and ACS Style
Dai, Z.-J.; Gao, J.; Ma, X.-B.; Kang, H.-F.; Wang, B.-F.; Lu, W.-F.; Lin, S.; Wang, X.-J.; Wu, W.-Y. Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy. Int. J. Mol. Sci. 2013, 14, 273-285.
Dai Z-J, Gao J, Ma X-B, Kang H-F, Wang B-F, Lu W-F, Lin S, Wang X-J, Wu W-Y. Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy. International Journal of Molecular Sciences. 2013; 14(1):273-285.
Dai, Zhi-Jun; Gao, Jie; Ma, Xiao-Bin; Kang, Hua-Feng; Wang, Bao-Feng; Lu, Wang-Feng; Lin, Shuai; Wang, Xi-Jing; Wu, Wen-Ying. 2013. "Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy." Int. J. Mol. Sci. 14, no. 1: 273-285.