Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer

Abnormal ion channel expression distinguishes several types of carcinoma. Here, we explore the relationship between voltage-gated sodium channels (VGSC) and epithelial ovarian cancer (EOC). We find that EOC cell lines express most VGSC, but at lower levels than fallopian tube secretory epithelial ce...

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Autores principales:	Iris S. Brummelhuis, Stephen J. Fiascone, Kathleen T. Hasselblatt, Gyorgy Frendl, Kevin M. Elias
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	high-grade serous ovarian cancer sodium channels local anesthetics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/835024f64c6d47a0aba2f1c716255950
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spelling	oai:doaj.org-article:835024f64c6d47a0aba2f1c7162559502021-11-11T15:31:59ZVoltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer10.3390/cancers132154372072-6694https://doaj.org/article/835024f64c6d47a0aba2f1c7162559502021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5437https://doaj.org/toc/2072-6694Abnormal ion channel expression distinguishes several types of carcinoma. Here, we explore the relationship between voltage-gated sodium channels (VGSC) and epithelial ovarian cancer (EOC). We find that EOC cell lines express most VGSC, but at lower levels than fallopian tube secretory epithelial cells (the cells of origin for most EOC) or control fibroblasts. Among patient tumor samples, lower <i>SCN8A</i> expression was associated with improved overall survival (OS) (median 111 vs. 52 months; HR 2.04 95% CI: 1.21–3.44; <i>p</i> = 0.007), while lower <i>SCN1B</i> expression was associated with poorer OS (median 45 vs. 56 months; HR 0.69 95% CI 0.54–0.87; <i>p</i> = 0.002). VGSC blockade using either anti-epileptic drugs or local anesthetics (LA) decreased the proliferation of cancer cells. LA increased cell line sensitivity to platinum and taxane chemotherapies. While lidocaine had similar additive effects with chemotherapy among EOC cells and fibroblasts, bupivacaine showed a more pronounced impact on EOC than fibroblasts when combined with either carboplatin (ΔAUC −37% vs. −16%, <i>p</i> = 0.003) or paclitaxel (ΔAUC −37% vs. −22%, <i>p</i> = 0.02). Together, these data suggest VGSC are prognostic biomarkers in EOC and may inform new targets for therapy.Iris S. BrummelhuisStephen J. FiasconeKathleen T. HasselblattGyorgy FrendlKevin M. EliasMDPI AGarticlehigh-grade serous ovarian cancersodium channelslocal anestheticsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5437, p 5437 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	high-grade serous ovarian cancer sodium channels local anesthetics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	high-grade serous ovarian cancer sodium channels local anesthetics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Iris S. Brummelhuis Stephen J. Fiascone Kathleen T. Hasselblatt Gyorgy Frendl Kevin M. Elias Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer
description	Abnormal ion channel expression distinguishes several types of carcinoma. Here, we explore the relationship between voltage-gated sodium channels (VGSC) and epithelial ovarian cancer (EOC). We find that EOC cell lines express most VGSC, but at lower levels than fallopian tube secretory epithelial cells (the cells of origin for most EOC) or control fibroblasts. Among patient tumor samples, lower <i>SCN8A</i> expression was associated with improved overall survival (OS) (median 111 vs. 52 months; HR 2.04 95% CI: 1.21–3.44; <i>p</i> = 0.007), while lower <i>SCN1B</i> expression was associated with poorer OS (median 45 vs. 56 months; HR 0.69 95% CI 0.54–0.87; <i>p</i> = 0.002). VGSC blockade using either anti-epileptic drugs or local anesthetics (LA) decreased the proliferation of cancer cells. LA increased cell line sensitivity to platinum and taxane chemotherapies. While lidocaine had similar additive effects with chemotherapy among EOC cells and fibroblasts, bupivacaine showed a more pronounced impact on EOC than fibroblasts when combined with either carboplatin (ΔAUC −37% vs. −16%, <i>p</i> = 0.003) or paclitaxel (ΔAUC −37% vs. −22%, <i>p</i> = 0.02). Together, these data suggest VGSC are prognostic biomarkers in EOC and may inform new targets for therapy.
format	article
author	Iris S. Brummelhuis Stephen J. Fiascone Kathleen T. Hasselblatt Gyorgy Frendl Kevin M. Elias
author_facet	Iris S. Brummelhuis Stephen J. Fiascone Kathleen T. Hasselblatt Gyorgy Frendl Kevin M. Elias
author_sort	Iris S. Brummelhuis
title	Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer
title_short	Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer
title_full	Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer
title_fullStr	Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer
title_full_unstemmed	Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer
title_sort	voltage-gated sodium channels as potential biomarkers and therapeutic targets for epithelial ovarian cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/835024f64c6d47a0aba2f1c716255950
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Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer

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