电压门控钠通道SCN5A/Nav1.5在卵巢癌中的表达及意义

Expression of voltage-gated sodium channel SCN5A/Nav1.5 in human ovarian cancer and its significance

目的:电压门控钠通道(voltage-gated sodium channels,VGSCs)与多种恶性肿瘤的转移过程密切相关。本研究探索VGSCs亚型SCN5A/Nav1.5在人卵巢癌中功能性表达的意义及其对卵巢癌细胞体外转移能力的影响。方法:通过SBFI荧光探针、免疫荧光、实时荧光定量PCR(real-time fluorogentic quantitative PCR,RFQ-PCR)、Western印迹、免疫组织化学、CCK-8Kit和Transwell小室法,分别检测卵巢癌SKOV-3细胞中Na+的分布、SCN5A/Nav1.5在分子和蛋白水平的表达及其与卵巢癌细胞体外迁移和侵袭能力的相关性。结果:在卵巢癌细胞SKOV-3和上皮性卵巢癌组织中存在SCN5A/Nav1.5的异常表达,30μmol/L河豚毒素(tetrodotoxin,TTX)能分别抑制SKOV-3细胞内Na+浓度、细胞体外迁移和侵袭力的(41.51±0.41)%、(33.80±1.6)%和(43.60±2.9)%,差异均有统计学意义(P<0.05)。结论:电压门控钠通道SCN5A/Nav1.5参与卵巢癌细胞的体外转移过程,并在卵巢癌的发生发展过程中起重要的作用,有可能成为卵巢癌治疗的靶标。

Objective：The different subtypes of voltage-gated sodium channels （VGSCs） are known to correlate with the migration of many malignant cancers. This study was to investigate the significance of functional expression of SCNSA/Nav1.5 in human ovarian cancer and its effects on migration capability of ovarian cancer cells in vitro. Methods： Sodium indicator SBFI and immunofluo-rescence method were used to detect the distribution of intracellular Na^＋. Real-time PCR, Western blotting, and immunohistochemistry were used to detect the mRNA and protein expression of SCN5A/Nav1.5. The effect of specific vohage-gated sodium channels inhibitor tetrodotoxin （TTX） on cell viability was measured by CCK-8 kit. The migration and invasion of ovarian cancer cell lines SKOV-3 were tested by Transwell chamber assay. Results： SCN5A/Nav1. 5 were over-expressed in ovarian cancer cell lines SKOV-3 and ovarian cancer specimens at mRNA and protein levels. TTX 30μmol/L inhibited the intracellular Na ＋ concentration by （41.51± 0.41）%. TTX also suppressed the invasion and migration capacities of SKOV-3 cells by （33.80±1.6）% and （43.60±2.9）%, respectively. The difference was significant （P 〈 0.05 ）. Conclusion：SCN5A/Nav1.5 is involved in the metastasis progression of ovarian cancer in vitro and plays an important role in the initiation and progression of ovarian cancer. It may become a target for ovarian cancer therapy.