Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer.
Voltage-gated sodium channels (VGSC) play important roles in the development and progression of many cancers. We report the possible roles of VGSC in human ovarian cancer. Relative mRNA expression levels of Nav1.1, Nav1.3, Nav1.4 and Nav1.5, analyzed by RT-PCR, were significantly higher in ovarian cancers cells compared with normal ovarian tissues; relative mRNA expression levels of Nav1.2, Nav1.4, Nav1.5 and Nav1.7 were significantly increased in highly metastatic ovarian cancer cells (Caov-3 and SKOV-3) compared with low-metastatic ovarian cancer cells (Anglne). Treatment of 30 microM tetrodotoxin reduced by 50-60% migration and invasion of Caov-3 and SKOV-3 without affecting proliferation. Real-time PCR, Western blot analysis and immunohistochemistry assays revealed that functional expression levels of Nav1.5 might be correlated with the grade and metastasis of ovarian cancer. Our findings suggested that abnormal expression of Nav1.5 could be an integral component of the metastatic process in human ovarian cancer and might serve as a therapeutic target in ovarian cancer treatment.
Gao
Rui
R
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China.
Shen
Yi
Y
Cai
Jing
J
Lei
Ming
M
Wang
Zehua
Z
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D015854:Up-Regulation; D055815:Young Adult
D014408:Biomarkers, Tumor; D009124:Muscle Proteins; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C568242:SCN1A protein, human; C424715:SCN3A protein, human; C106251:SCN4A protein, human; C568320:SCN5A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin