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Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy

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Author(s): Zhi-Jun Dai | Jie Gao | Xiao-Bin Ma | Hua-Feng Kang | Bao-Feng Wang | Wang-Feng Lu | Shuai Lin | Xi-Jing Wang | Wen-Ying Wu

Journal: International Journal of Molecular Sciences
ISSN 1422-0067

Volume: 14;
Issue: 1;
Start page: 273;
Date: 2012;
Original page

Keywords: pancreatic carcinoma | rapamycin | mTOR | anti-tumor | apoptosis | autophagy

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.

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