Effects of volume-activated chloride channels on the invasion and migration of human endometrial cancer cells

Objective: To investigate the role of volume-activated chloride channels (VACC) in invasion and migration of human endometrial cancer cell. Materials and Methods: Expression of voltage-gated chloride channel-3 (CLC-3) was detected by employing reverse transcriptase-polymerase chain reaction (RT-PCR) in human endometrial cancer Ishikawa cell line. Cell invasion and cell migration were determined by using the Transwell invasion and migration assay, respectively. NPPB, a Cl– channel blocker, was treated to observe the effects of volume-activated Cl– channel on invasion and migration of endometrial cancer cell. Results: CLC-3 RNA expression was observed in Ishikawa cell line. The authors showed that blockade of Cl– channels specifically inhibited invasion and migration of endometrial cancer Ishikawa cell line in a dose-dependent manner. VACC activation and subsequent regulatory volume decrease (RVD) were markedly suppressed by NPPB. Anion replacement studies indicate that permeation of Cl– ions through endometrial cancer Cl– channel is obligatory for regulatory volume decrease (RVD) induced by VACC. Moreover, [Ca2+]i measurements indicated that VACC-mediated increase in [Ca2+]i was one of the mechanisms of cancer cell invasion and migration. Conclusions: These data intensely suggest that VACC in endometrial cancer may facilitate tumor invasion and migration, presumably through inducing RVD and mediating [Ca2+]i increase.

Chloride channels; Invasion; Migration; Endometrial cancer.

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