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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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.