Impaired actin filaments decrease cisplatin sensitivity via dysfunction of volume-sensitive Cl^- channels in human...

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Cisplatin is a crucial chemotherapy agent, but cancer cells develop resistance.
• Loss of volume-sensitive outwardly rectifying (VSOR) chloride channels is linked to cisplatin resistance.

Purpose of the Study:

• To investigate the role of actin filaments and VSOR channels in cisplatin resistance of human epidermoid carcinoma cells.

Main Methods:

• Compared protein expression and actin filament organization in cisplatin-sensitive (KB) and resistant (KCP-4) cells.
• Utilized β-actin knockdown and cytochalasin D treatment to disrupt actin filaments.
• Assessed VSOR chloride currents and the regulatory volume decrease (RVD) process.

Main Results:

• KB cells showed higher β-actin expression and more organized actin filaments than KCP-4 cells.
• β-actin knockdown and cytochalasin D treatment reduced VSOR currents and slowed RVD.
• Cytochalasin D also inhibited cisplatin-induced apoptosis in KB cells.

Conclusions:

• Disruption of actin filaments leads to VSOR channel dysfunction.
• VSOR channel dysfunction contributes to cisplatin resistance in human epidermoid carcinoma cells.