p53基因、 Fas/FasL在提高肝癌细胞化疗药物敏感性中的作用

目的：探讨野生型p53(wtp53)、Fas/FasL在提高肝癌细胞化疗药物敏感性中的作用及其机制。方法：用化疗药物争光霉素600mg/L分别处理人肝癌细胞株HepG2、Hep3B和PLC／PRF／5，观察争光霉素对肝癌细胞Fas/FasL表达的影响；预先将携带wtp53基因的重组腺病毒分别感染人肝癌细胞株24h，再用争光霉素进行诱导，观察感染前后肝癌细胞Fas/FasL的表达变化，并对经上述处理前后的肝癌细胞进行凋亡检测。结果：单纯争光霉素600mg/L诱导虽可提高肝癌细胞FasL的表达，但对其Fas的表达并无明显作用；感染wtp53基因后再应用争光霉素（600mg/L），则肝癌细胞Fas/FasL的表达水平不仅显著高于单纯争光霉素组，同时自身也发生了明显凋亡。结论：wtp53基因可能是通过上调肝癌细胞Fas/FasL的表达来降低其自身的凋亡阈值，进而提高肝癌细胞对化疗药物的敏感性，Fas/FasL在wtp53基因逆转肝癌细胞耐药性中具有一定的作用。

The role of wtp53 and Fas/FasL in the process of sensitizing hepatoma cells to chemotherapy

Objective To investigate the role of p53 and Fas/FasL in the process of sensitizing hepatoma cells to chemotherapy.Methods Human hepatoma cell lines HepG2,Hep3B and PLC/PRF/5 were treated respectively with a chemotherapeutic drug (bleomycin) at various concentrations (0 600?mg/L).The expression of Fas/FasL in hepatoma cell lines was detected after treatment with bleomycin or in combination with infection with a recombinant adenoviral vector expressing wide type (wt) p53 gene (Ad p53).Then,effect of Fas/FasL on the apoptosis in hepatoma cell lines themselves was examined.Results Bleomycin(0 600?mg/L)did not suppress the growth of hepatoma cell lines,and the same dosage had a stimulatory effect on FasL and no apparent regulation of Fas.However,treatment with bleomycin following infection with Ad p53 could significantly increase the expression of Fas/FasL in the hepatoma cell lines and therefore render these cells more sensitive to chemotherapeutic drug via Fas mediated apoptosis,compared to single chemotherapy.Conclusion Apoptosis induced by bleomycin is mediated in part by wt p53 dependent stimulation of Fas/FasL system and reverse the hepatoma cell's drug resistance.The Fas/FasL may play a role in the reversal effects of the drug resistant hepatoma cell lines by wtp53.