白细胞介素-23通过无翅基因相关整合位点/β-连环蛋白通路增强舌鳞状细胞癌抗凋亡及耐药能力

Interleukin-23 strengthens the anti-apoptotic and drug resistance of human tongue squamous cell carcinoma through the Wingless-related integration site/β-catenin pathway

目的检测白细胞介素-23(IL-23)在舌鳞状细胞癌组织中表达水平与临床预后的关系,研究舌鳞状细胞癌细胞系SCC9经IL-23处理后抗凋亡及耐药能力的变化。方法免疫组织化学法检测28例舌鳞状细胞癌患者组织中IL-23的表达情况;实时定量聚合酶链反应(q RT-PCR)检测不同浓度的IL-23处理后,SCC9中无翅基因相关整合位点(Wnt)1及c-myc的m RNA表达水平;结合小分子干扰RNA(si RNA),Western blot法检测IL-23对SCC9细胞的β-连环蛋白(β-catenin)和B淋巴细胞瘤-2(Bcl-2)、三磷酸腺苷结合转运蛋白G超家族成员2(ABCG2)、P-糖蛋白(P-gp)表达影响及潜在机制;甲基噻唑基四唑法检测SCC9细胞在IL-23作用下对顺铂的抗凋亡能力改变。结果舌鳞状细胞癌组织中IL-23表达强度与淋巴结转移、神经侵犯及治疗复发有相关性(P<0.05);IL-23可增强癌细胞抗凋亡蛋白Bcl-2和耐药相关蛋白ABCG2、P-gp的表达,并且与Wnt通路活化程度密切相关;IL-23能够显著加强SCC9细胞对顺铂的抵抗性(P<0.01)。结论 IL-23通过上调舌鳞状细胞癌细胞的Wnt通路增强其抗凋亡及耐药能力。

ObjectiveThis study aims to detect the expression level of interleukin-23 （IL-23） in tongue squamous cell carcinoma tissues and its relationship with clinical prognosis, as well as explore the anti-apoptotic and drug resistance of the tongue squamous cell line-SCC9 before and after treatment with IL-23. Methods The expression of IL-23 in tumor tissues from 28 tongue cancer patients was analyzed by immunohistochemistry assay. Quantitative real-time polymerase chain reac-tion （qRT-PCR） was used to detect the mRNA expression of Wingless-related integration site （Wnt）1 and c-myc in SCC9 cells treated with different IL-23 concentrations. After interferencing the β-catenin with small interfering RNA （siRNA）, the expres-sion of β-catenin, B-cell lymphoma-2 （Bcl-2）, ATP-binding cassette sub-family G member 2 （ABCG2）, and permeability-glycoprotein （P-gp） in SCC9 was measured by Western blot analysis. The effect of IL-23 on the apoptotic resistance of SCC9 to cisplatin was examined by methyl thiazolyl tetrazolium test. Results The expression of IL-23 in tongue cancer tissues was correlated with lymphatic metastasis, nerve invasion, and the recurrence after therapy （P〈0.05）. After dealing with IL-23, SCC9 showed the upregulation effect of Bcl-2, ABCG2 and P-gp expressions. IL-23 was closely related to the activation level of the Wnt pathway and significantly strengthened the resistance to cisplatin （P〈0.01）. Conclusion IL-23 activates the Wnt pathway in tongue squamous cell carcinoma, thereby enhancing its resistance to apoptosis and drug.