Abstract 514: Targeting of Voltage-gated sodium channel NaV1.5 inhibits cell proliferation and colony formation in breast and ovarian cancer cells.

Abstract

Abstract Breast cancer is the most common and the second leading cause of death in women worldwide while ovarian cancer is the leading cause of gynecological cancers. Breast and ovarian cancer cells have increased proliferation, invasion/metastasis and resistance to programmed cell death due to mutations, altered signaling pathways and deregulated of control mechanism. One of the differences between normal and cancer cells is the changes in the regulation and the function of ion channels. Ion channels are important signaling molecules expressed in a wide range of tissues where they have significant involvement in determining a variety of cellular functions: solute transport, volume control, enzyme activity, secretion, invasion, gene expression, excitation-contraction coupling and intercellular communication. During the malignant transformation, a series of genetic alterations occur, which may also affect the expression and activity of ion channels. This abnormal ion channel activity has been hypothesized to support cell proliferation and tumor growth. Voltage-gated sodium channels (VGNaC) are classically described as critical elements of action potential initiation and propagation in excitable cells. Recent studies showed that VGNaC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGNaC activity potentiated cellular directional motility, endocytosis and invasion. However, the mechanisms of the VGNaC and its functional relevance to breast cancer proliferation are currently not well-known. In this study, we investigated that the effects of downregulation NaV1.5 channel expression by specific RNA interference (ie siRNA) in breast and ovarian cancer cells in vitro. In our work, we first determined the effects of Adult NaV1.5 siRNA and analyzed the effects of Adult and Neonatal (neonatal splice variant of NaV1.5) NaV1.5 silencing by siRNA in BCa cells by Real-Time PCR. Our Real-Time PCR results showed that Adult NaV1.5 channel siRNA reduced the level of NaV1.5 mRNA for MDA-MB-231 BCa cells. We found that knockdown of NaV1.5 channel by siRNA significantly inhibited MDA-MB-231 breast and SKOV3-IP1, SKOV3-TR and HEYA8 ovarian cancer cell proliferation and colony formation. We are currently investigating downstream cellular pathways involved in NaV1.5 mediated proliferation and other cellular functions. In conclusion, our results demonstrate that targeting of NaV1.5 in breast and ovarian cancer cells decreases cell proliferation and colony formation and it may be used as a new therapeutic target in these cancers. Citation Format: Mumin A. Erdogan, Bulent Ozpolat. Targeting of Voltage-gated sodium channel NaV1.5 inhibits cell proliferation and colony formation in breast and ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 514. doi:10.1158/1538-7445.AM2013-514