Impaired actin filaments decrease cisplatin sensitivity via dysfunction of volume-sensitive Cl- channels in human epidermoid carcinoma cells

被引：5

作者：

Shimizu, Takahiro ^{[1
]}

Fujii, Takuto ^{[1
]}

Ohtake, Hironao ^{[1
]}

Tomii, Toshie ^{[1
]}

Takahashi, Ryuta ^{[1
]}

Kawashima, Kentaro ^{[1
]}

Sakai, Hideki ^{[1
]}

机构：

[1] Univ Toyama, Fac Pharmaceut Sci, Dept Pharmaceut Physiol, Sugitani 2630, Toyama 9300194, Japan

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2020年 / 235卷 / 12期

关键词：

actin filaments; apoptosis; cell volume; chloride channels; cisplatin; ACTIVATED CHLORIDE CURRENT; ANION CHANNELS; MOLECULAR-MECHANISMS; ESSENTIAL COMPONENT; LRRC8; HETEROMERS; MEMBRANE-PROTEIN; RESISTANCE; IDENTIFICATION; CONTRIBUTES; MODULATION;

D O I：

10.1002/jcp.29767

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cisplatin is a widely used platinum-based anticancer drug in the chemotherapy of numerous human cancers. However, cancer cells acquire resistance to cisplatin. So far, functional loss of volume-sensitive outwardly rectifying (VSOR) Cl- channels has been reported to contribute to cisplatin resistance of cancer cells. Here, we analyzed protein expression patterns of human epidermoid carcinoma KB cells and its cisplatin-resistant KCP-4 cells. Intriguingly, KB cells exhibited higher beta-actin expression and clearer actin filaments than KCP-4 cells. The beta-actin knockdown in KB cells decreased VSOR Cl- currents and inhibited the regulatory volume decrease (RVD) process after cell swelling. Consistently, KB cells treated with cytochalasin D, which depolymerizes actin filaments, showed smaller VSOR Cl- currents and slower RVD. Cytochalasin D also inhibited cisplatin-triggered apoptosis in KB cells. These results suggest that the disruption of actin filaments cause the dysfunction of VSOR Cl- channels, which elicits resistance to cisplatin in human epidermoid carcinoma cells.

引用

页码：9589 / 9600

页数：12