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 of TGF-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.
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siRNA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 mRNA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siRNA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。.