Chloride channel-3 is required for efficient tumour cell migration and invasion in human cervical squamous cell carcinoma.

OBJECTIVE: Chloride channel-3 (ClC-3) plays significant roles in various physiological and physiopathological activities, including cell migration and invasion ability. The purpose of this study was to evaluate whether ClC-3 influences the migration and invasion of cervical squamous cell carcinoma cells and its possible mechanisms.

METHODS: Paraffin-embedded cervical tissues, including normal cervical tissues, cervical squamous cell carcinoma (SCC) and homologous paracancerous tissues, were collected. The cervical squamous cell carcinoma and matched paracarcinoma fresh tissues specimens were collected from 49 patients with SCC, and the normal cervical tissues were collected from 45 non-cervical squamous cell carcinoma patients. The human cervical squamous carcinoma cell line SiHa was cultured. ClC-3 expression was assessed by real-time RT-PCR, immunohistochemistry and Western blot, and the expression of phospho-PI3K/Akt/mTOR and matrix metalloproteinase-9 (MMP-9) was detected by Western blot. Small interfering RNA (siRNA) technology was used to knockdown ClC-3 expression. SiHa cell migration and invasion ability were measured using Transwell assays with or without Matrigel-coated membranes.

RESULTS: ClC-3 mRNA and protein expression in SCC tissues from cervical squamous cell carcinoma patients was significantly upregulated, and no significant difference was noted between the matched paracarcinoma fresh tissue from the same patients and non-cervical cancer patients. SiHa cell migration and invasion and phospho-PI3K/Akt/mTOR and MMP-9 expression were attenuated by knocking down ClC-3 expression using ClC-3 siRNA.

CONCLUSIONS: ClC-3 participates in the processes of SCC cell migration and invasion and regulates MMP-9 expression via the PI3K/Akt/mTOR signaling pathway.