期刊文献+

雷帕霉素抑制人前列腺癌细胞增殖及其作用机制 被引量:5

Rapamycin inhibited the proliferation of prostate carcinoma cell line PC-3M-2B4 in vitro
原文传递
导出
摘要 目的观察雷帕霉素(Rapamycin)对体外培养的人前列腺癌PC-3M-2134细胞增殖及凋亡的影响,探讨其机制。方法分别用不同浓度的雷帕霉素(100、200、400、800μg/L)对细胞进行干预后,采用噻唑蓝(MTT)比色法检测细胞增殖变化,流式细胞术检测细胞凋亡变化,Westernblot法检测凋亡相关蛋白bcl-2及hax表达的变化。结果雷帕霉素能明显抑制PC-3M-21M细胞的增殖活性,此作用呈现量-效、时-效关系。雷帕霉素呈浓度依赖性诱导细胞凋亡。雷帕霉素作用PC-3M-21t4细胞后,细胞内凋亡抑制蛋白bcl-2的表达明显降低,bax蛋白的表达明显增加。结论雷帕霉素能够通过调节凋亡相关蛋白bcl-2和bax的表达比例,诱导前列腺癌细胞凋亡,从而抑制肿瘤生长。 Objective To investigate the effects of Rapamycin on the growth and apoptosis of human prostate carcinoma cell line PC-SM-21M. Methods The inhibitory effect of Rapamycin was observed at 100,200,400,800μg/L on the growth of human prostate carcinoma cell line PC-3M-2B4 in serum-free medium for different concentrations by methyl thiazol tetrazolium (M3W) assays. Flow cytometry (FCM) analysis was used to study the changes of cell apoptosis. The expression level of bcl-2 and bax was determined by Western blotting. Results Rapamycin caused dose-dependent inhibition on the growth of human prostate carcinoma cell line PC-3M-2B4 in a concentration-and time dependent manner. Rapamycin induced the apoptosis of PC-SM-2B4 cells in a concentration-dependent manner. The levels of bcl-2 protein were reduced gradually with the increase of concentration or action time. Conclusion Rapamycin, a mTOR inhibitor, inhibits the growth of human prostate cancer cell and induces apoptosis of human prostate cancer cell. mTOR might be a potential target for anti-prostate cancer.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2011年第1期124-126,共3页 Chinese Journal of Experimental Surgery
基金 湖北省自然科学基金资助项目(2007ABA285)
关键词 哺乳动物雷帕霉素靶蛋白 雷帕霉素 BCL-2 凋亡 信号通路 mTOR Rapamycin bcl-2 Apoptosis Signal pathway
  • 相关文献

参考文献9

  • 1Sehgal SN.Sirolimus:its discovery,biological properties,and mechanism of action.Transplant Proc,2003,35:7-14.
  • 2Akselband Y,Harding MW,Nelson PA.Rapamycin inhibits spontaneous and fibroblast growth factor beta-stimulated proliferation of endothelial cells and fibroblasts.Transplant Proc,1991,23:2833-2837.
  • 3Gregory CR,Pratt RE,Huie P,et al.Effects of treatment with cyclosporine,FK506,rapamycin,mycophenolic acid,or deoxyspergualin on vascular muscle proliferation in vitro and in vivo.Transplant Proc,1993,25:770-771.
  • 4Chan S,Scheulen ME,Johnston S,et al.Phase 2 study f two dose levels of CCI-779 in locally advanced or metastatic breast cancer (MBC)failing prior anthracycline and/or taxane regimens.Proc Asco,2003,22:774.
  • 5Hudes G,Carducci M,Tomczak P,et al.A phase Ⅲ,randomized,3-arm study of temsirolimus (TEMSR)or interferon-a(IFN) or the combination of TEMSR + IFN in the treatment of first-line,poor risk patients with advanced renal cell carcinoma (adv RCC).Proc Am Soc Clin Oncol,2006,24:2.
  • 6Noh WC,Mondesire WH,Peng J,et al.Determinants of rapamycin sensitivity in breast cancer cells.Clin Cancer Res,2004,10:1013-1023.
  • 7Edwards J,Krishna NS,Witton CJ,et al.Gene Amplifications Associated with the Development of Hormone-Resistant Pros tate Cancer.Clin Cancer Res,2003,9:5271-5281.
  • 8Gustin JA,Maehama T,Dixon JE,et al.The PTEN tumor suppressor protein inhibits tumor necrosis factor-induced nuclear factor κB activity.J Biol Chem,2001,276:27740-27744.
  • 9Nicholson KM,Anderson NG.The protein kinase B/Akt signaling pathway in human malignancy.Cell Signal,2002,14:381-395.

同被引文献50

  • 1Scott KL, Kabbarah O, Liang MC, et al. GOLPH3 modulatesimTOR signalling and rapamycin sensitivity in cancer. Nature, 2009, 459: 1085-1090.
  • 2Wang JH,Chen XT,Wen ZS,et al. High expression of GOLPH3 in e- sophageal squamous cell carcinoma correlates with poor prognosis. PLoS One,2012,7 :e45622.
  • 3Zeng Z, Lin H, Zhao X, et al. Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Clin Cancer Res ,2012,18:4059-4069.
  • 4Li XY, Liu W, Chen SF, et al. Expression of the Golgi phosphoprotein- 3 gene in human gliomas:a pilot study. J Neurooncol,2011,105 :159- 163.
  • 5Zhou J, Xu T, Qin R, et al. Overexpression of Golgi phosphoprotein-3 ( GOLPH3 ) in glioblastoma multiforme is associated with worse prog- nosis. J Neuroonco1,2012 ,110 : 195-203.
  • 6Scott KL, Chin L. Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis. Clin Cancer Res, 2010,16:2229-2234.
  • 7All MF, Chachadi VB, Petrosyan A, et al. Golgi phosphoprotein 3 de- termines cell binding properties under dynamic flow by controlling Golgi localization of Core 2 N-acetylglucosaminyltransferase 1. J Biol Chem,2012,287 : 39564 -39577.
  • 8Kunigou O, Nagao H, Kawabata N, et al. Role of GOLPH3 and GOL- PH3L in the proliferation of human rhabdomyosarcoma. Oncol Rep, 2011,26 : 1337-1342.
  • 9SCOTr K L,CABBALA O,LIANG M C,et al. GOLPH3 modulates roTOR signalling and rapamycin sensitivity in cancer[ J]. Nature ,2009,459 : 1085-1090.
  • 10HU B S, HU H, ZHU C Y, et al. Overexpression of GOL- PH3 is associated with poor clinical outcome in gastric cancer[J]. Tumour Biol,2013,34:515-520.

引证文献5

二级引证文献23

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部