IL-18通过调节TRPV4/Smad7信号通路促进皮肤鳞状细胞癌的增殖

目的:探讨白介素18(Interleukin-18,IL-18)对皮肤鳞状细胞癌(Cutaneous Squamous Cell Carcinoma,CSCC)增殖的影响及可能分子机制。方法:采用外源性IL-18刺激皮肤鳞状细胞癌A431细胞和Colo-16细胞24 h、48 h和72 h,通过CCK-8检测细胞的增殖能力;48 h后qRT-PCR和Western blot检测刺激前后瞬时感受器电位离子通道家族蛋白4(Transient Receptor Potential Vanilloid 4,TRPV4)和Smad7以及p-Smad7的表达。外源性IL-18刺激皮肤鳞状细胞癌A431细胞和Colo-16细胞12 h后,采用TRPV4激动剂G3给药处理A431细胞和Colo-16细胞36 h,通过MMT检测细胞增殖能力,qRT-PCR和Western blot检测刺激前后TRPV4的表达和Smad7以及p-Smad7的表达。结果:外源性IL-18刺激A431细胞和Colo-16细胞可显著促进其增殖,抑制TRPV4的表达而激活p-Smad7的表达;TRPV4激动剂G3可以部分抵消外源性IL-18对A431细胞和Colo-16细胞的增殖作用。结论:IL-18可能通过下调TRPV4激活Smad7信号通路促进皮肤鳞状细胞癌增殖作用。

IL-18 Promotes Proliferation of Cutaneous Squamous Cell Carcinoma by Regulating TRPV4/Smad7 Signaling Pathway

ABSTRACT Objective: To investigate the effect of interleukin-18 (IL-18) on the proliferation of Cutaneous Squamous Cell Carcinoma (CSCC) and its possible molecular mechanism. Methods: Exogenous IL-18 was used to stimulate skin squamous cell carcinoma A431 cells and Colo-16 cells for 24 h, 48 h and 72 h. The proliferation of cells was detected by CCK-8. After 48 h stimulation by qRT-PCR and western blot, expression of transient receptor potential vanilloid 4 (TRPV4) and Smad7, p-Smad7. After exogenous IL-18 stimulated squamous cell carcinoma A431 cells and Colo-16 cells for 12 h, A431 cells and Colo-16 cells were treated with TRPV4 agonist G3 for 36 h. Cell proliferation was detected by MMT, qRT- The expression of TRPV4 and the expression of Smad7 and p-Smad7 were detected by PCR and Western blot. Results: Exogenous IL-18 stimulated A431 cells and Colo-16 cells to significantly promote proliferation, inhibit TRPV4 expression and activate p-Smad7 expression. TRPV4 agonist G3 partially offsets exogenous IL-18, proliferation of A431 cells and Colo-16 cells. Conclusion: IL-18 promotes the proliferation of squamous cell carcinoma of the skin , it may be related to the down-regulation of TRPV4 and activation of Smad7 signaling pathway.