TGF-β1磷酸化Smad4调控结直肠癌对奥沙利铂的反应性  

TGF-β1 regulates the sensitivity of colorectal cancer cells to oxaliplatin by phosphorylating Smad4

作　　者：申连东[1] 曹光材[1] 齐文海[1] 左春义 白江江 胡海峰[2] 董明清 SHEN Lian-dong;CAO Guang-cai;QI Wen-hai;ZUO Chun-yi;BAI Jiang-jiang;HU Hai-feng;DONG Ming-qing(Department of Anus and Intestine Surgery,Affiliated Hospital of Yanan University,Yanan 716000,China;Department of Oncology,Affiliated Hospital of Yanan University,Yanan 716000,China;Basic Medical College of Air Force Military Medical University,Xi'an 710032,China)

机构地区：[1]延安大学附属医院肛肠外科,陕西延安716000 [2]延安大学附属医院肿瘤科,陕西延安716000 [3]空军军医大学基础医学院,陕西西安710032

出　　处：《中国中西医结合消化杂志》2020年第6期437-443,共7页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：陕西省自然科学基金项目(No:2013JM4016)。

摘　　要：[目的]探究转化生长因子β1(TGF-β1)通过靶向其下游基因SMAD家族成员4(Smad4),调节结直肠癌细胞对奥沙利铂敏感性的机制研究。[方法]根据结直肠患者对奥沙利铂的敏感性将其分为耐药组以及非耐药组,采用ELISA检测患者血清中TGF-β1的表达量,采用免疫组化检测患者体内Smad4磷酸化水平。采用Western blot检测结直肠癌细胞中Smad4磷酸化水平的变化,采用CCK8检测结直肠癌细胞增殖能力的变化。[结果]结直肠癌患者血清中TGF-β1表达量高于正常组(P<0.001),耐药组患者血清中TGF-β1的表达量高于非耐药组(P<0.001)。癌组织中Smad4磷酸化水平高于癌旁组织(P<0.001),且耐药组患者癌组织Smad4磷酸化水平高于非耐药组(P<0.001)。Pearson相关性分析显示耐药组血清中的TGF-β1表达水平与Smad4磷酸化程度呈正相关性。进一步证实TGF-β1刺激可增加结直肠癌细胞的耐药性;敲减Smad4后,结直肠癌细胞的耐药性下降。[结论]TGF-β1可通过靶向Smad4调控结直肠癌细胞对奥沙利铂的耐药性。[Objective]To explore the mechanism of transforming growth factor beta-1-like(TGF-β1)regulating the sensitivity of colorectal cancer cells to oxaliplatin by targeting its downstream gene SMAD family member 4(Smad4).[Methods]According to the sensitivity of colorectal patients to oxaliplatin,patients were divided into drug-resistant group and non-drug-resistant group.The expression of TGF-β1 in serum was detected by enzyme-linked immunosorbent assay,and the level of Smad4 phosphorylation was detected by immunohistochemistry.Western blot was used to detect the phosphorylation of Smad4 in colorectal cancer cells,and CCK8 was used to detect the proliferation of colorectal cancer cells.[Results]The expression of serum TGF-β1 in patients with colorectal cancer was higher than that in normal group(P<0.001),and the expression of serum TGF-β1 in drug-resistant group was higher than that in non-drug-resistant group(P<0.001).Smad4 phosphorylation level in cancer tissue was higher than that in adjacent tissues(P<0.001),and Smad4 phosphorylation level in drug-resistant group was higher than that in non-drug-resistant group(P<0.001).Pearson correlation analysis showed that the expression of TGF-β1 in serum of drug-resistant group was positively correlated with the phosphorylation level of Smad4.It was further confirmed that the stimulation of TGF-β1 could increase the drug resistance of colorectal cancer cells,and the drug resistance of colorectal cancer cells decreased after knocking down Smad4.[Conclusion]TGF-β1 can regulate the resistance of colorectal cancer cells to oxaliplatin by targeting Smad4.

关 键 词：结直肠癌 TGF-Β1 SMAD4 奥沙利铂 耐药 

分 类 号：R445.1[医药卫生—影像医学与核医学]