非小细胞肺癌耐药相关基因表达与细胞凋亡相关性及其临床意义

The Correlation between Multidrug Resistance Related Gene and Apoptosis of Lung Cancer and Its Clinical Significance

目的：探讨非小细胞肺癌Non－Small Cell Lung Cancer NSCLC多种耐药相关基因MRP、MDR1、c－erbB－2表达与细胞凋亡及相关基因bc1－2、c－myc的关系与意义。方法：RT－PCR、免疫组化分析多种耐药、凋亡相关基因mRNA及蛋白表达，原位末端标记Terminal deoxynucleotidyl transferaseTdT－mediated biotin dUTP nick end－labelingTUNEL检测凋亡细胞。结果：63例NSCLC MRP、MDR1、c－erbB－2、bc1－2、c－myc mRNA阳性率分别为81．0％51／63、38．1％24／63、47．6％30／63、65．1％41／63、76．2％48／63，均高于相应的蛋白表达水平分别为74．6％、34．9％、46．0％、61．9％、71．4％，二者具高度相关性相关系数r＝＋0．76以上P＜0．02，5例癌旁组织仅2例c－myc弱阳性，余皆阴性。c－myc、bc1－2与c－erbB－2呈正相关r＝＋0．54P＝0．001r＝＋0．48P＝0．023，与MRP、MDR1无相关性。凋亡指数与bc1－2负相关r＝－0．58P＝0．017，与MRP、MDR1、c－erbB－2、c－myc无相关性；腺癌及鳞癌化疗有效组凋亡指数均数27．2±2．130．5±1．8高于化疗无效组9．4±1．312．6±2．4P＝0．001P＝0．004，bcl－2、MRP、c－erbB－2阳?

Objective To study the correlation between the expressions of multidrug resistance MDR gene MRP MDR1 c－erbB－2 and apoptosis related genes bcl－2 c－myc and its clinical significance in non－small cell lung cancer． Methods RT－PCR and immunohistochemistry were used to examine expressions of mRNA and protein of the above mentioned genes apoptotic cells were evaluated by terminal deoxynucleotidyl transferase TDT－mediated biotin dUTP nick end－labeling TUNEL Results The levels of MRP MDR1 c－erbB－2 bcl－2 and c－myc mRNA 81．0％ 38．1％ 47．6％ 65．1％ 76．2％ were higher than the levels of their corresponding proteins 74．6％ 34．9％ 46．0％ 61．9％ 71．4％ respectively and their significant positive associations were found between mRNA levels and their protein expression r＞0．764P＜0．02 in 63 analysed samples positive correlations were demonstrated between c－myc and c－erbB－2 r＝＋0．54P＝0．001 bcl－2 and c－erbB－2 r＝＋0．48P＝0．023． No significant correlation was found between bcl－2 and MRP or MDR1 in NSCLC． Apoptotic index was observed to be inversely correlated with bcl－2 expression r＝－0．58P＝0．017 but not to be associated with MRP MDR1 c－erbB－2 or c－myc． There were higher apoptotic index and lower expressions of MRP bcl－2 and c－erbB－2 in the effective groups to chemotherapy than in the ineffective groups P＜0．05． Patients with expressions of more than three MDR and／or apoptosis related genes had shorter median survival time P＝0．01． Conclusion Multidrug resistance in NSCLC may be involved in the co－operation of multiple MDR and／or apoptosis related genes and which relates to median survival time．