Abstract
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.
MeSH terms
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Adult
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Aged
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Blotting, Western
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Dose-Response Relationship, Drug
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Immunohistochemistry
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Middle Aged
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Muscle Proteins / antagonists & inhibitors
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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NAV1.1 Voltage-Gated Sodium Channel
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NAV1.3 Voltage-Gated Sodium Channel
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NAV1.4 Voltage-Gated Sodium Channel
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NAV1.5 Voltage-Gated Sodium Channel
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Neoplasm Invasiveness
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Neoplasm Staging
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism*
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Ovarian Neoplasms / pathology
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sodium Channel Blockers / pharmacology
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Sodium Channels / genetics
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Sodium Channels / metabolism*
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Tetrodotoxin / pharmacology
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Up-Regulation
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Young Adult
Substances
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Biomarkers, Tumor
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Muscle Proteins
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NAV1.1 Voltage-Gated Sodium Channel
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NAV1.3 Voltage-Gated Sodium Channel
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NAV1.4 Voltage-Gated Sodium Channel
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NAV1.5 Voltage-Gated Sodium Channel
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Nerve Tissue Proteins
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RNA, Messenger
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SCN1A protein, human
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SCN3A protein, human
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SCN4A protein, human
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SCN5A protein, human
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Sodium Channel Blockers
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Sodium Channels
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Tetrodotoxin