转化生长因子β1在调节小细胞肺癌耐药细胞对化学治疗药物耐药性中的作用及临床意义

Role of TGF-β1 in multi-drug resistance in small cell lung cancer and its clinical significance

目的:探讨转化生长因子β1(transforming growth factor β1,TGF-β1)在调节小细胞肺癌多药耐药中的作用,并分析其表达与临床预后的关系。方法:采用实时荧光定量PCR法及Western印迹检测小细胞肺癌敏感细胞株H69和耐药细胞株H69AR中TGF-β1的表达,应用si RNA抑制耐药细胞株H69AR中的TGF-β1表达,采用CCK8检测细胞对各种化学治疗药物的敏感性;应用实时荧光定量PCR及免疫组织化学方法检测小细胞肺癌患者组织标本及癌旁组织中TGF-β1的表达,并分析TGF-β1与小细胞肺癌患者预后的关系。结果:与细胞株H69比较,TGF-β1 m RNA在细胞株H69AR中的表达升高了(5.93±0.47)倍(t=8.986,P<0.01);TGF-β1蛋白在细胞株H69AR中的表达明显增加了(8.49±1.92)倍(t=4.127,P<0.01)。转染si RNA后,细胞株H69AR中TGF-β1的表达下降了70.432%(F=21.20,P<0.01);细胞对化学治疗药物的敏感性增加(t=4.576,P<0.05);与癌旁组织比较,TGF-β1在小细胞肺癌组织中的表达明显增高(t=13.925,P<0.01)。TGF-β1的表达与疾病的分期、患者的生存时间及化学治疗的敏感性有关(均P<0.05);与患者的性别、年龄无关(均P>0.05)。结论:TGF-β1参与了调节小细胞肺癌的多药耐药,TGF-β1可作为评估小细胞肺癌化学治疗敏感性及临床预后的潜在靶基因。

Objective： To investigate the role of transforming growth factor β1 （TGF-β1） in multi-drug resistance in small cell lung cancer and its clinical significance. Methods： The mRNA and protein expressions of TGF-β1 in H69 and H69AR cells were detected by real-time PCR and Western blot, respectively. After silence of TGF-β1, the sensitivity of H69AR to drugs was detected by CCK8 assay. The expressions ofTGF-β1 in lung cancer and paracarcinoma tissues were examined by QRT-PCR and immunohistochemistry. The relationship of TGF-β1 expression with clinical pathological features and prognosis of patients was studied. Results： Compared to H69, the mRNA and protein expressions of TGF-β1 in H69AR cells were significantly increased by （5.93±0.47） and （8.49±1.92） folds, respectively （P〈0.01）. Transfection of TGF-β1 siRNA resulted in a decrease of TGF-β1 expression by 70.432% in H69AR cells （F=21.20, P〈0.01） and an increase insensitivity to chemotherapeutic agents of H69AR cells （t=4.576, P〈0.05）. Compare with the paracarcinoma tissues, the expression of TGF-β1 was significantly increased in small cell lung cancer tissues （t=13.925, P〈0.01）, which was closely related with clinical stage, chemosensitivity and overall survival （all P〈0.05）, but not related with gender, age （both P〉0.05）. Conclusion： TGF-β1 is involved in the regulation of small cell lung cancer multidrug resistance, which may be a potential marker to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.