• 中山大學(xué)附屬第三醫(yī)院肝移植中心（廣州510630）;

目的 　觀察雷帕霉素(rapamycin,RAPA)體外對(duì)肝癌細(xì)胞Bel-7402的生長(zhǎng)抑制和誘導(dǎo)凋亡作用， 并探討線粒體在誘導(dǎo)凋亡機(jī)理中的作用。
方法 　以5、10、20、30、40和 50 nmol/L不同濃度的RAPA作用于體外培養(yǎng)的Bel-7402細(xì)胞，MTT法檢測(cè)細(xì)胞生長(zhǎng)抑制率； 應(yīng)用流式細(xì)胞儀檢測(cè)細(xì)胞凋亡； Hoechst 33258熒光染色法觀察細(xì)胞凋亡時(shí)的形態(tài)學(xué)變化； JC-1染色法檢測(cè)細(xì)胞線粒體膜電位（mitochondrial membrane potential）的變化。
結(jié)果 　RAPA可顯著地抑制Bel-7402的生長(zhǎng)，誘導(dǎo)細(xì)胞發(fā)生凋亡, 并呈現(xiàn)出明顯的量-效與時(shí)-效關(guān)系，50 nmol/L RAPA作用72 h，引起的細(xì)胞抑制率和凋亡率明顯高于其他濃度藥物組（P＜0.01）。RAPA作用Bel-7402細(xì)胞48 h后，在Hoechst 33258熒光染色圖片上可見(jiàn)細(xì)胞核濃縮、細(xì)胞核碎裂等典型的細(xì)胞凋亡特征。凋亡過(guò)程中線粒體膜電位下降。
結(jié)論 　RAPA能抑制Bel-7402細(xì)胞的生長(zhǎng)，誘導(dǎo)細(xì)胞凋亡發(fā)生，線粒體膜電位下降在凋亡過(guò)程中可能起到重要作用。

引用本文： 張俊峰,陳規(guī)劃,陸敏強(qiáng),蔡常潔,楊揚(yáng),李華. 線粒體在雷帕霉素誘導(dǎo)肝癌細(xì)胞Bel-7402凋亡中的作用. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007, 14(3): 280-283. doi: 復(fù)制

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  2. 2. Boffa DJ, Luan F, Thomas D, et al. Rapamycin inhibits the gr-owth and metastatic progression of non-small cell lung cancer [J]. Clin Cancer Res， 2004; 10(1 Pt 1)∶293.
  3. 3. Granger DK, Cromwell JW, Chen SC, et al. Prolongation of renal allograft survival in a large animal model by oral rapamycin monotherapy [J]. Transplantation， 1995; 59(2)∶183.
  4. 4. Kreis H, Cisterne JM, Land W, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients [J]. Transplantation， 2000; 69(7)∶1252.
  5. 5. Wiedmann MW, Caca K. Molecularly targeted therapy for gastrointestinal cancer [J].Curr Cancer Drug Targets， 2005; 5(3)∶171.
  6. 6. Rathmell WK, Wright TM, Rini BI. Molecularly targeted therapy in renal cell carcinoma [J]. Expert Rev Anticancer Ther， 2005; 5(6)∶1031.
  7. 7. Newmeyer DD, Farschon DM, Reed JC. Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria [J].Cell， 1994; 79(2)∶353.
  8. 8. Alano CC, Beutner G, Dirksen RT, et al. Mitochondrial permeability transition and calcium dynamics in striatal neurons upon intense NMDA receptor activation [J]. J Neurochem， 2002; 80(3)∶531.
  9. 9. Hengartner MO. The biochemistry of apoptosis [J]. Nature， 2000; 407(6805)∶770.