SRGN′s interaction with TGFβ promote the chemoresistence of NSCLC
10.3760/cma.j.cn431274-20200506-00563
- VernacularTitle:小分子糖蛋白SRGN与TGFβ相互作用促进非小细胞肺癌的化疗耐药
- Author:
Ting LIU
1
;
Wei GUO
;
Meijun LIU
;
Zhijie ZHANG
;
Xiaoting JIA
;
Jiang YIN
;
Zhimin HE
Author Information
1. 广州医科大学附属肿瘤医院肿瘤研究所，广州市恶性肿瘤转化医学重点实验室 510095
- From:
Journal of Chinese Physician
2020;22(5):651-655,661
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of small molecule glycoprotein Serglycin (SRGN) in chemotherapy resistance of non-small cell lung cancer (NSCLC).Methods:In NSCLC H1299 cell line, shRNA technology was used to interfere with the expression of SRGN and establish stable interfering cell line. Western blot and real time fluorescence quantitative polymerase chain reaction (qRT-PCR) were used to verify the knockdown efficiency; MTS was used to detect the knockdown cell line′s drug sensitivity to cDDP and Oxaliplatin; enzyme linked immunosorbent assay (ELISA), Western blot and qRT-PCR were used to explore the effect of transforming growth factor β (TGFβ) on SRGN and vice versa; Western blot was used to detect the effect of SRGN on epithelial-mesenchymal transition (EMT) related molecules, and online data bioinformatics was used to analyze the correlation between SRGN and EMT related molecules expression; in addition, online prognostic analysis software (kmplot) was used to analyze the correlation between SRGN, TGFβ and prognosis of lung cancer patients.Results:Comparing with the control group, the test group, knocking down SRGN can obviously improve the drug sensitivity of NSCLC cell to cDDP ( P=0.032 7) or Oxaliplatin ( P=0.014 2). TGFβ can enhance the experission of SRGN in NSCLC and SRGN also can help TGFβ secreted from cells. SRGN promotes the epithelial mesenchyme transition by modulating Snail1. By analyzing TCGA database, we found that the expression of SRGN was negatively correlated with the expression of CDH1 (coding for Ecadherin protein) ( r=-0.25) and there was a positive correlation with Snai1 expression ( r=0.37). These results suggest that SRGN can promote the change of EMT in lung cancer cells through TGF β 1 and snail 1. The overall survival time of NSCLC patients with low expression of SRGN was much longer than the patients with high expression of SRGN ( P=0.007 7). The overall survival time of NSCLC patient with low expression in both SRGN and TGFβ1 or TGFβ2 was 73months or 42.8 months longer than that with high expression in both SRGN and TGFβ1/2. Conclusions:Intercting with TGFβ1, SRGN promotes EMT of NSCLC cells, which facilitates the chemoresistence of NSCLC. The simultaneous low expression of SRGN and TGFβ1 or TGFβ2 can significantly prolong the overall survival of patients with NSCLC.
