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目的:探讨小分子糖蛋白丝甘蛋白聚糖(SRGN)在非小细胞肺癌(NSCLC)化疗耐药中的作用。方法:在非小细胞肺癌H1299细胞株中，采用shRNA技术干扰SRGN的表达并建立稳定干扰细胞株，并用Western blot技术和实时荧光定量PCR(qRT-PCR)验证敲低效率；采用MTS方法检测稳定敲低SRGN的肺癌细胞株对化疗药物顺铂和奥沙利铂的药物敏感性；采用ELISA、Western blot及qRT-PCR检测转化生长因子β(TGFβ)对SRGN表达的影响，以及SRGN介导TGFβ细胞外分泌的作用；采用Western blot检测SRGN对上皮间质转化(EMT)相关分子的影响，以及采用在线数据生物信息学分析SRGN与EMT相关分子表达的相关性；此外采用在线预后分析软件(kmplot)分析SRGN、TGFβ与肺癌患者预后的相关性。结果:与对照组比较，敲低SRGN可明显增强NSCLC细胞对化疗药物顺铂(n P＝0.032 7)和奥沙利铂(n P＝0.014 2)的敏感性；TGFβ可促进NSCLC细胞中SRGN的表达，并且SRGN可促进TGFβ的细胞外分泌；SRGN可通过Snail1促进NSCLC细胞的EMT改变，分析TCGA数据库，发现在NSCLC癌组织标本中SRGN表达与CDH1(编码Ecadherin蛋白)表达呈负相关(n r＝－0.25)，而与SNAI1表达呈正相关(n r＝0.37)；SRGN低表达的NSCLC患者相比高表达的患者总生存期明显延长(n P＝0.007 7，平均中位生存时间延长15.9个月)，而同时SRGN与TGFβ1或TGFβ2低表达的患者中位生存时间分别延长73个月或42.8个月。n 结论:SRGN与TGFβ1相互作用，促进肺癌细胞EMT改变，进而促进肺癌细胞的化疗耐药。SRGN与TGFβ1或TGFβ2同时低表达可显著延长非小细胞肺癌患者总生存期。“,”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 (n P=0.032 7) or Oxaliplatin (n 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) (n r=-0.25) and there was a positive correlation with Snai1 expression (n 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 ( n 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.n 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.