非小细胞肺癌组织及细胞中IL-35的表达
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摘要
目的探讨白细胞介素35(IL-35)在非小细胞肺癌组织和细胞中的表达及其对肺癌细胞生物学功能的影响。方法免疫组化法检测IL-35在74例非小细胞肺癌组织中的表达,分析IL-35表达与非小细胞肺癌临床病理特征的相关性;RT-PCR法检测IL-35在不同肺癌细胞中的表达水平;CCK-8法、划痕试验和Transwell实验分别检测IL-35对细胞增殖和迁移侵袭能力的影响。结果免疫组化和RT-PCR检测结果表明,IL-35在非小细胞肺癌组织的表达水平明显上调(P<0.05),在肺癌细胞系中均有不同程度表达。IL-35表达与肿瘤分期、淋巴结转移成正相关(P<0.05),与患者性别、年龄、组织类型、分化程度及远端转移等均无相关性(P>0.05)。外源性IL-35的刺激作用促进肺癌细胞的增殖和迁移侵袭。结论 IL-35在非小细胞肺癌组织和细胞中高表达,并促进肺癌细胞的增殖与迁移侵袭,可以作为临床肺癌基因治疗的靶向指标。
Objective To investigate the expression of interleukin-35(IL-35) in non-small cell lung cancer tissues and cells and its effect on the biological function of lung cancer cells.Methods Immunohistochemistry was used to detect the expression of IL-35 in 74 non-small cell lung cancer tissues, and the correlation between IL-35 expression and clinicopathological features of non-small cell lung cancer was analyzed. RT-PCR was used to detected the expression of IL-35 in different lung cancer cell lines. The proliferation, migration and invasion ability of cells were assessed by CCK-8 assay, Scratch assay and Transwell assay after the stimulation of IL-35, respectively.Results The result of immunohistochemistry showed that IL-35 expression was significantly up-regulated in non-small cell lung cancer tissues(P<0.05), and RT-PCR found that IL-35 was expressed on lung cancer cell lines with different degrees. The expression of IL-35 was positively correlated with tumor stage and lymph node metastasis(P<0.05). However, it was not related with gender, age, tissue type, differentiation degree and distant metastasis(P>0.05). The stimulation of exogenous IL-35 promoted the proliferation, migration and invasion of lung cancer cells.Conclusion IL-35 is highly expressed in non-small cell lung cancer tissues and cells, and promotes the proliferation, migration and invasion of lung cancer cells. It can be used as a target for clinical gene therapy of lung cancer.
Objective To investigate the expression of interleukin-35(IL-35) in non-small cell lung cancer tissues and cells and its effect on the biological function of lung cancer cells.Methods Immunohistochemistry was used to detect the expression of IL-35 in 74 non-small cell lung cancer tissues, and the correlation between IL-35 expression and clinicopathological features of non-small cell lung cancer was analyzed. RT-PCR was used to detected the expression of IL-35 in different lung cancer cell lines. The proliferation, migration and invasion ability of cells were assessed by CCK-8 assay, Scratch assay and Transwell assay after the stimulation of IL-35, respectively.Results The result of immunohistochemistry showed that IL-35 expression was significantly up-regulated in non-small cell lung cancer tissues(P<0.05), and RT-PCR found that IL-35 was expressed on lung cancer cell lines with different degrees. The expression of IL-35 was positively correlated with tumor stage and lymph node metastasis(P<0.05). However, it was not related with gender, age, tissue type, differentiation degree and distant metastasis(P>0.05). The stimulation of exogenous IL-35 promoted the proliferation, migration and invasion of lung cancer cells.Conclusion IL-35 is highly expressed in non-small cell lung cancer tissues and cells, and promotes the proliferation, migration and invasion of lung cancer cells. It can be used as a target for clinical gene therapy of lung cancer.
引文
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[2] 汪硕敏,顾康生.血清癌胚抗原、铁蛋白和糖基抗原199在非小细胞肺癌诊断中的临床价值[J].安徽医科大学学报,2018,53(9):1444-7.
[3] Wang R X,Yu C R,Dambuza I M,et al.Interleukin-35 induces regulatory B cells that suppress autoimmune disease[J].Nat Med,2014,20(6):633-41.
[4] Long J,Guo H,Cui S,et al.IL-35 expression in hepatocellular carcinoma cells is associated with tumor progression[J].Oncotarget ,2016,7(29):45678-86.
[5] Huang C,Li N,Li Z,et al.Tumour-derived interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression[J].Nat Commun,2017,8(1):14035-49.
[6] Ma Y,Chen L,Xie G,et al.Elevated level of interleukin-35 in colorectal cancer induces conversion of T cells into iTr35 by activating STAT1/STAT3[J].Oncotarget,2016,7(45):73003-15.
[7] 许良中,杨文涛.免疫组织化学反应结果的判定标准[J].中国癌症杂志,1996,6(4):229-31.
[8] 陈晴晴,束军,谢庆书,等.二甲双胍丁酸盐对人肺腺癌A549细胞增殖、凋亡与迁移能力的影响[J].安徽医科大学学报,2018,53(2):171-5.
[9] Teixid C,Karachaliou N,Gonz Lez-Cao M,et al.Erratum to as-says for predicting and monitoring responses to lung cancer immunotherapy[J].Cancer Biol Med,2015,12(2):87-95.
[10] 李晓东,杨小龙.白细胞介素12与消化系统肿瘤的相关性[J].医学综述,2014,20(11):1977-9.
[11] 黄崇标,田野,崔焱,等.白细胞介素35的在肿瘤发展中的作用[J].中国肺癌杂志,2016,19(4):230-5.
[12] Wang Z,Liu J Q,Liu Z,et al.Tumor-derived IL-35 promotes tumor growth by enhancing myeloid cell accumulation and angiogenesis[J].J Immunol,2013,190(5):2415-23.
[13] Tao Q,Pan Y,Wang Y,et al.Regulatory T cells-derived IL-35 promotes the growth of adult acute myeloid leukemia blasts[J].Int J Cancer,2015,137(10):2384-93.
[14] Gu X,Tian T,Zhang B,et al.Elevated plasma interleukin-35 levels predict poor prognosis in patients with non-small cell lung cancer[J].Tumour Biol,2015,36(4):2651-6.