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Clinical Research
A novel transient receptor potential calcium channel subfamily V member 6 (TRPV6): Its expression and clinical significance in stomach cancer
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Abstract:
Objective: To study the expression and putative role of a novel transient receptor potential calcium channel subfamily V member 6 (TRPV6) in stomach cancer. Methods： Sixty-five pairs of tumor and surrounding tissue specimens were collected from patients with pathologically confirmed stomach cancer who underwent surgical resection in our hospital between May, 2010 and March, 2013. TRPV6 protein in these specimens was assessed by immunohistochemical SP staining. To evaluate the putative functional role for TRPV6 in stomach cancer, human stomach cancer MGC-803 cells were treated with 2-amino ethyl two phenyl boronic acid (2-APB), a TRPV6 channel blocker. After treatment, cell proliferation, apoptosis and migration were assessed by CCK-8 assay, flow cytometry and transwell assay, respectively, and TRPV6, AKT/p-AKT, p-GSK3 protein contents were analyzed by Western blotting. Results: TRPV6 protein was detected in 95.4% (62/65) of cancerous tissue specimens but only in 36.9% (24/65) of the corresponding non-cancerous tissue specimens (P<0.01). Immunoreactive TRPV6 signal was positively associated with the tumor size, lymph, distant metastasis and Dukes stage (P<0.05). The TRPV6 blocker 2-APB significantly inhibited MGC-803 cell proliferation, induced MGC-803 cell apoptosis and inhibited MGC-803 cell migration (P<0.05). Moreover, 2-APB treatment resulted in significant decreases in TRPV6, p-AKT, and p-GSK3β proteins in a dose-dependent manner in MGC-803 cells (P<005). Conclusions: TRPV6 is highly expressed in stomach cancer, where it promotes cancer cell proliferation and inhibits cancer cell apoptosis. Down-regulation of p-AKT, p-GSK-3 β protein expressions may be possible mechanisms underlying the tumorigenic activity of TRPV6.
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