PMID- 23344033 OWN - NLM STAT- MEDLINE DCOM- 20150831 LR - 20220321 IS - 1422-0067 (Print) IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 14 IP - 1 DP - 2012 Dec 21 TI - Antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy. PG - 273-85 LID - 10.3390/ijms14010273 [doi] AB - 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. FAU - Dai, Zhi-Jun AU - Dai ZJ AD - Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China. dzj0911@126.com. FAU - Gao, Jie AU - Gao J FAU - Ma, Xiao-Bin AU - Ma XB FAU - Kang, Hua-Feng AU - Kang HF FAU - Wang, Bao-Feng AU - Wang BF FAU - Lu, Wang-Feng AU - Lu WF FAU - Lin, Shuai AU - Lin S FAU - Wang, Xi-Jing AU - Wang XJ FAU - Wu, Wen-Ying AU - Wu WY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121221 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antineoplastic Agents) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (BECN1 protein, human) RN - 0 (Beclin-1) RN - 0 (Membrane Proteins) RN - 0 (RNA, Messenger) RN - 0 (bcl-2-Associated X Protein) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - I9N81SC5HD (monodansylcadaverine) RN - L90BEN6OLL (Cadaverine) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/*drug effects MH - Apoptosis Regulatory Proteins/genetics/metabolism MH - Autophagy/*drug effects MH - Beclin-1 MH - Cadaverine/analogs & derivatives/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Shape/drug effects MH - Flow Cytometry MH - Humans MH - Membrane Proteins/genetics/metabolism MH - Mice MH - NIH 3T3 Cells MH - Pancreatic Neoplasms/*pathology/ultrastructure MH - RNA, Messenger/genetics/metabolism MH - Sirolimus/*pharmacology MH - TOR Serine-Threonine Kinases/genetics/metabolism MH - Vacuoles/drug effects/metabolism/ultrastructure MH - bcl-2-Associated X Protein/genetics/metabolism PMC - PMC3565263 EDAT- 2013/01/25 06:00 MHDA- 2013/01/25 06:01 PMCR- 2013/01/01 CRDT- 2013/01/25 06:00 PHST- 2012/11/07 00:00 [received] PHST- 2012/12/02 00:00 [revised] PHST- 2012/12/12 00:00 [accepted] PHST- 2013/01/25 06:00 [entrez] PHST- 2013/01/25 06:00 [pubmed] PHST- 2013/01/25 06:01 [medline] PHST- 2013/01/01 00:00 [pmc-release] AID - ijms14010273 [pii] AID - ijms-14-00273 [pii] AID - 10.3390/ijms14010273 [doi] PST - epublish SO - Int J Mol Sci. 2012 Dec 21;14(1):273-85. doi: 10.3390/ijms14010273.