肺腺癌细胞的STAT3信号传导途径的研究

STUDY ON SIGNAL TRANSDUCER PATHWAY OF STAT3 IN LUNG ADENOCARCINOMA

目的:探明STAT3在肺腺癌细胞中增殖分化、抗凋亡作用与耐药之间的关系。方法:采用浓度梯度递增法诱导A549细胞株形成耐药细胞系,免疫组化及蛋白印迹法联合检测A549及耐药株中STAT3、LRP、MRP蛋白表达情况。结果:成功诱导了A549/CARP耐药细胞株。免疫组化:A549组、A549/CARP组STAT3阳性细胞数无显著性差异(P>0.05);LRP、MRP阳性细胞数有显著性差异(P<0.01);STAT3、LRP、MRP之间表达均无相关性(P>0.05)。蛋白印迹:A549组、A549/CARP组均存在STAT3蛋白的表达,二者无差异性(P>0.05);STAT3、LRP、MRP之间表达均无相关性(P>0.05)。结论:STAT3参与了肺腺癌细胞的增殖分化和抗凋亡作用,并未参与介导肺腺癌的耐药;LRP、MRP均参与了诱导肺腺癌的耐药,但二者之间无相关性;LRP、MRP介导的耐药机制与STAT3信号传导途径无关;可通过破坏STAT3信号传导来控制肿瘤细胞的生长和增殖,为肺癌的治疗提供了以STAT3为靶向的基因治疗。

Objective： To elucidate the relationship of signal transducer and activator of transcription 3 （STAT3） to hyperplasia and differentiation,anti-apoptosis and drug resistance in lung adenocarcinoma. Methods： CARP-resistant A549 （A549/CARP） was developed by means of different dosages and the sensitivity of anticancer drugs was screened in the A549/CARP by MTT method. Immunohistochemical and Westem-blotting detection of STAT3 lung resistance-related protein（LRP） and multiple resistance protein（MRP） were carried out in A549 and A549/CARP. Results： Resistant subline A549/CARP was established. Immunohistochemistry：There was no significant difference in the expression of STAT3 between A549 and A549/CARP （P〉0.05）. There was signifcant difference in the expression of LRP and MRP between A549 and A549/CARP（P〈0.01）.The expression of STAT3 is not correlated with LRP and MRP （/9〉0.05）. Westem-blotting：There was no significant difference in the expression of STAT3 in A549 and A549/CARP（P〉0.05）. The expression of STAT3 is not correlated with LRP and MRP（P〉0.05）. Conclusion： The overexpression of LRP and MRP in drug-resistance cell subline and low expression in adenocarcinoma may play a positive role in drug resistance.The drug resistant mechanism of LRP and MRP was not correlated with the pathway of STAT3. It is suggested that STAT3 may play a positive role in hyperplasia, differentiation and anti-apoptosis,but not in drug resistance, which will contribute to study further of treatment of lung carcinoma.