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 β‐actin expression and clearer actin filaments than KCP‐4 cells. The β‐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.

中文翻译：

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肌动蛋白丝受损可通过人表皮样癌细胞中体积敏感的Cl-通道功能障碍降低顺铂敏感性。

顺铂是广泛用于铂的抗癌药物，可用于多种人类癌症的化学疗法。然而，癌细胞获得对顺铂的抗性。到目前为止，体积敏感外向整流（VSOR）的Cl功能丧失^-信道已被报道有助于癌细胞对顺铂抗性。在这里，我们分析了人类表皮样癌KB细胞及其顺铂耐药性KCP-4细胞的蛋白表达模式。有趣的是，与KCP-4细胞相比，KB细胞表现出更高的β-肌动蛋白表达和更清晰的肌动蛋白丝。在KB细胞中的β肌动蛋白敲除降低VSOR氯^-电流并抑制细胞肿胀后调节体积减少（RVD）过程。一致的是，与细胞松弛素d，其中解聚肌动蛋白丝处理KB细胞，表明较小VSOR氯^-电流和较慢RVD。细胞松弛素D也抑制顺铂触发的KB细胞凋亡。这些结果表明，的肌动蛋白丝的破坏引起VSOR Cl组成的功能障碍^-信道，其引起在人表皮样癌细胞顺铂耐药。