Liu Huanxin, Wang Wei, Zhang Guoxiang, Guo Linlang
Department of Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China.
Department of Pathology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Apr 28;42(4):419-425. doi: 10.11817/j.issn.1672-7347.2017.04.009.
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.
探讨转化生长因子β1(TGF-β1)在小细胞肺癌多药耐药中的作用及其临床意义。方法:分别采用实时荧光定量PCR和蛋白质免疫印迹法检测H69和H69AR细胞中TGF-β1的mRNA和蛋白表达。沉默TGF-β1后,采用CCK8法检测H69AR细胞对药物的敏感性。采用QRT-PCR和免疫组织化学法检测肺癌组织和癌旁组织中TGF-β1的表达。研究TGF-β1表达与患者临床病理特征及预后的关系。结果:与H69相比,H69AR细胞中TGF-β1的mRNA和蛋白表达分别显著增加(5.93±0.47)倍和(8.49±1.92)倍(P<0.01)。转染TGF-β1 siRNA后,H69AR细胞中TGF-β1表达降低70.432%(F=21.20,P<0.01),对化疗药物的敏感性增加(t=4.576,P<0.05)。与癌旁组织相比,小细胞肺癌组织中TGF-β1的表达显著增加(t=13.925,P<0.01),与临床分期、化疗敏感性和总生存期密切相关(均P<0.05),但与性别、年龄无关(均P>0.05)。结论:TGF-β1参与小细胞肺癌多药耐药的调控,可能是评估小细胞肺癌化疗敏感性和临床预后的潜在标志物。