Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Int J Mol Sci. 2019 May 30;20(11):2663. doi: 10.3390/ijms20112663.
Cells possess the capability to adjust their volume for various physiological processes, presumably including cell proliferation and migration. The volume-regulated anion channel (VRAC), formed by LRRC8 heteromers, is critically involved in regulatory volume decrease of vertebrate cells. The VRAC has also been proposed to play a role in cell cycle progression and cellular motility. Indeed, recent reports corroborated this notion, with potentially important implications for the VRAC in cancer progression. In the present study, we examined the role of VRAC during cell proliferation and migration in several cell types, including C2C12 myoblasts, human colon cancer HCT116 cells, and U251 and U87 glioblastoma cells. Surprisingly, neither pharmacological inhibition of VRAC with 4-[(2-Butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid (DCPIB), carbenoxolone or 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB), nor siRNA-mediated knockdown or gene knockout of the essential VRAC subunit LRRC8A affected cell growth and motility in any of the investigated cell lines. Additionally, we found no effect of the VRAC inhibition using siRNA treatment or DCPIB on PI3K/Akt signaling in glioblastoma cells. In summary, our work suggests that VRAC is dispensable for cell proliferation or migration.
细胞具有根据各种生理过程调整其体积的能力，推测包括细胞增殖和迁移。由 LRRC8 异源二聚体形成的体积调节阴离子通道（VRAC）在脊椎动物细胞的调节性体积减少中起着关键作用。VRAC 也被认为在细胞周期进程和细胞运动中发挥作用。事实上，最近的报道证实了这一观点，这对 VRAC 在癌症进展中的作用具有重要意义。在本研究中，我们研究了 VRAC 在几种细胞类型（包括 C2C12 成肌细胞、人结肠癌细胞 HCT116 以及 U251 和 U87 神经胶质瘤细胞）中的增殖和迁移过程中的作用。令人惊讶的是，用 4-[(2-丁基-6,7-二氯-2-环戊基-2,3-二氢-1-氧代-1H-茚-5-基)氧基]丁酸（DCPIB）、蟾毒灵或 5-硝基-2-(3-苯基丙基-氨基)苯甲酸（NPPB）抑制 VRAC 的药理学方法，siRNA 介导的敲低或必需的 VRAC 亚基 LRRC8A 的基因敲除均未影响任何研究细胞系中的细胞生长和迁移。此外，我们发现使用 siRNA 处理或 DCPIB 抑制 VRAC 对神经胶质瘤细胞中的 PI3K/Akt 信号没有影响。总之，我们的工作表明 VRAC 对于细胞增殖或迁移是可有可无的。
