Yu Wenfa, Wang Ping, Ma Huiming, Zhang Guozheng, Yulin Zhao, Lu Baocai, Wang Huiming, Dong Mingmin
Clin Lab. 2014;60(4):621-8. doi: 10.7754/clin.lab.2013.130614.
Despite the tight correlation between T-type Ca2+ channels and a great variety of tumors, the roles of alpha1G subunit of T-type Ca2+ channels in laryngeal squamous cell carcinoma (LSCC) have not yet been investigated.
In the present study, we examined the expression of alpha1G subunit of T-type Ca2+ channel in human LSCC tissues and cell lines. One human laryngeal squamous cell carcinoma cell line, Hep-2, was also examined for T-type channels using voltage-clamp recordings. Cell proliferation assays were performed in the presence or absence of T-type channel blocker mibefradil and alpha1G subunit sepcific siRNA. The cell cycle was determined by flow cytometry.
Our results indicated that the a1G subunit of T-type Ca2+ channel is highly expressed in human laryngeal squamous cell carcinoma tissues and cell lines. alpha1G siRNA significantly down-regulated the protein expression of the alpha1G subunit. Both alpha1G siRNA and mibefradil inhibited Hep-2 cell proliferation and arrested cell cycle progression.
Together, these findings suggest a functional role of T-type channels in certain laryngeal carcinomas, and that inhibition of T-type channels reduces cell proliferation via cell cycle arrest, suggesting that the alpha1G subunit of T-type Ca2+ channel may be used as a therapeutic target for treating LSCC.
尽管T型Ca2+通道与多种肿瘤之间存在紧密关联,但T型Ca2+通道的α1G亚基在喉鳞状细胞癌(LSCC)中的作用尚未得到研究。
在本研究中,我们检测了T型Ca2+通道α1G亚基在人LSCC组织和细胞系中的表达。使用电压钳记录法对一种人喉鳞状癌细胞系Hep-2的T型通道进行了检测。在存在或不存在T型通道阻滞剂米贝地尔和α1G亚基特异性siRNA的情况下进行细胞增殖测定。通过流式细胞术确定细胞周期。
我们的结果表明,T型Ca2+通道的α1G亚基在人喉鳞状细胞癌组织和细胞系中高表达。α1G siRNA显著下调了α1G亚基的蛋白表达。α1G siRNA和米贝地尔均抑制Hep-2细胞增殖并阻止细胞周期进程。
总之,这些发现表明T型通道在某些喉癌中具有功能性作用,并且抑制T型通道可通过细胞周期阻滞减少细胞增殖,这表明T型Ca2+通道的α1G亚基可能用作治疗LSCC的治疗靶点。