In the present study, we found that E3Ab specifically bound to Nav1
In the present study, we found that E3Ab specifically bound to Nav1. 5 in ovarian malignancy cells and inhibited tumor growth and invasion, indicating the therapeutic potential of E3Ab in Nav1.5-positive ovarian cancer. Increasing evidence showed that Nav1.5 was over-expressed in cancers and was implicated in tumor metastasis cascade (3-5). a peptide specific polyclonal antibody realizing E3 of Nav1.5, which could inhibit approximately 60% of Na+ current in HEK-293 and Chinese hamster ovary epithelia cells upon an extra-cellular application, without effecting Rabbit Polyclonal to RPL19 Nav1.4 and Nav1.6 isoforms (12). The aim of this study was to investigate the inhibitory effect of E3Ab on malignancy cells and control. E3Ab, third extracellular region antibody. E3Ab inhibits ovarian malignancy cell invasion, migration, and proliferation all P 0.05). The migration- and invasion-suppressing effect of E3Ab in malignancy cells was comparable to that induced by lidocaine. Moreover, EdU assays revealed that this cell proliferation activity was reduced by 29.1%, 32.1%, and 24.4% in SiHa, MDA-MB-231, and Cavo-3 cells, respectively (all P 0.05). In addition, the MMP-9 protein expression was reduced by E3Ab and lidocaine as revealed by Western blot assays (control. E3Ab, third extracellular region antibody; EdU, 5-Ethynyl-2′-deoxyuridine; MMP-9, metal matrix protease-9. Conversation Therapeutic antibodies specifically binding to tumor surface antigens have improved the treatment for a wide range of cancers (15). In the present study, we found that E3Ab specifically bound to Nav1.5 in ovarian cancer cells and inhibited tumor growth and invasion, indicating the therapeutic potential of E3Ab Monoammoniumglycyrrhizinate in Nav1.5-positive ovarian cancer. Increasing evidence showed that Nav1.5 was over-expressed in cancers and was implicated in tumor metastasis cascade (3-5). For example, Nav1.5 was found to be up-regulated in breast cancer tissues compared with matched non-cancer breast tissue as well as in a highly metastatic cell line MDA-MB-231 compared with a poorly metastatic cell line MCF-7 (16). In an orthotopic breast cancer model, functionally active Nav1.5 contributed to tumor growth, local invasion, and metastasis to liver, lungs and spleen (17). Similarly, Nav1.5 expression was significantly increased in human colon cancer specimens compared with normal colon tissues. Moreover, ropivacaine, lidocaine, TTX, and a siRNA specifically targeting Nav1.5 could inhibit Nav1.5 channel function and invasion of metastatic colon cancer SW620 cells, and the Nav1.5 channel activator veratridine promoted SW620 cell invasion (9,18). In astrocytomas, increased Nav1.5 expression was positively correlated with the degree of malignancy and Nav1. 5 knock-down significantly suppressed tumor cell proliferation, migration and invasion (19). In our previous study, high Nav1.5 was associated with metastatic house in ovarian malignancy (8). However, the function of Nav1.5 in malignancy remains largely unexplored. In the present study, we found specific blockage of Nav1.5 could inhibit cancer growth and invasive capacity, suggesting a tumor-promoting role and therapeutic implication of Nav1.5 in ovarian cancer. We found that blocking Nav1.5 by E3Ab inhibited migration and invasion properties of cancer cells, accompanied by decreased MMP-9 protein levels. However, the mechanisms through which Nav1.5 promotes tumor metastasis in ovarian malignancy remains less investigated. House recognized Nav1.5 as a key regulator of a gene transcriptional network that controls colon cancer invasion, including genes regulating Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process, and cell cycle control (18). Nav1.5 and Na(+)/H(+) exchanger type 1 (NHE-1) were functionally coupled and expressed at the sites of matrix remodeling in invadopodia of breast cancer cells. The Na+ current carried by Nav1.5 increased the NHE-1 dependent H+ efflux and enhanced tumor Monoammoniumglycyrrhizinate invasion by promoting extra-cellular matrix degradation (20,21). In addition, siRNA knockdown of Nav1.5 could reduce invasion of endocrine-resistant breast cancer cells, in part through reducing ERK1/2 phosphorylation and total MMP Monoammoniumglycyrrhizinate activity (22). Similarly, in a previous study, we found that blockade of Nav1.5 channel activity in breast cancer MDA-MB-231 cells resulted in a significant decrease in MMP-9 expression and cell invasion property (23). These findings implicate Nav1.5 in multiple mechanisms of tumor invasion and metastasis. In the present study, we used a subcutaneous xenograft model to assess the anti-tumor effects of E3Ab and lidocaine. Subcutaneous xenograft model is the most widely used model for drug screening, because it is simple to operate, high performing, and easy to monitor. However, there are some limitations of this model when compared to an orthotopic tumor model. In an orthotopic ovarian malignancy.