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Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer
1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China.
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.
Insights
Voltage-gated sodium channels (VGSC) are upregulated in ovarian cancer, promoting cell migration and invasion. Nav1.5 expression correlates with cancer grade and metastasis, suggesting it as a potential therapeutic target for ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Channelopathies
Background:
- Voltage-gated sodium channels (VGSC) are implicated in cancer development and progression.
- Their specific roles in human ovarian cancer require further elucidation.
Purpose of the Study:
- To investigate the expression and functional significance of VGSC in human ovarian cancer.
- To determine the correlation between VGSC expression and clinicopathological features, including metastasis and grade.
Main Methods:
- RT-PCR and real-time PCR for mRNA expression analysis.
- Western blot and immunohistochemistry for protein expression analysis.
- Tetrodotoxin treatment to assess functional impact on cell migration and invasion.
Main Results:
- Significantly higher mRNA expression of Nav1.1, Nav1.3, Nav1.4, and Nav1.5 in ovarian cancer cells versus normal tissues.
- Increased mRNA levels of Nav1.2, Nav1.4, Nav1.5, and Nav1.7 in highly metastatic ovarian cancer cells.
- Tetrodotoxin treatment inhibited migration and invasion by 50-60% without affecting proliferation.
- Functional Nav1.5 expression correlated with ovarian cancer grade and metastasis.
Conclusions:
- Abnormal Nav1.5 expression is linked to the metastatic process in human ovarian cancer.
- Nav1.5 may serve as a potential therapeutic target for ovarian cancer treatment.
