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

Abstract

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.