School of Medicine and Health Sciences Poster Presentations

Title

Repurposing of ligand-gated anionic channel therapeutics to inhibit tumor cell function

Document Type

Poster

Keywords

oncology; ion channels; proliferative pathways; inhibitory pathways

Publication Date

4-2017

Abstract

Oncogenic behavior has been shown to be directly influenced by the activity of voltage- and ligand-gated ion channels of the oncogenic cell. We have previously demonstrated that upregulated expression of voltage-gated sodium channel (VGSC) SCN5A in SW620 and SW480 human colon cancer cells is associated with activity-dependent enhanced invasive ability, which can be suppressed by siRNA-mediated knockdown or pharmacological inactivation (e.g. lidocaine, ropivacaine). As it remains unknown whether dysregulated VGSC expression in oncogenic cells enhances proliferative/metastatic potential by stimulating oncogenic signaling pathways, suppressing inhibitory pathways, or a combination of both, the focus of this study was to determine the status of signal transduction pathways following ion channel activation and/or inhibition. We hypothesized that upregulated VGSC expression enhances proliferative ability by stimulating oncogenic pathways and suppressing inhibitory pathways. By pharmacological activation of the over-expressed VGSCs in SW620 and SW480 human colon cancer cell lines, we concluded that VGSC activation resulted in both stimulative oncogenic signaling and suppressed inhibitory signaling, which were more consistently observed in the SW620 cell line vs SW480 cell line and more noticeable at 48h post-treatment vs 24h post-treatment.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

1

Comments

Poster to be presented at GW Annual Research Day 2017

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Repurposing of ligand-gated anionic channel therapeutics to inhibit tumor cell function

Oncogenic behavior has been shown to be directly influenced by the activity of voltage- and ligand-gated ion channels of the oncogenic cell. We have previously demonstrated that upregulated expression of voltage-gated sodium channel (VGSC) SCN5A in SW620 and SW480 human colon cancer cells is associated with activity-dependent enhanced invasive ability, which can be suppressed by siRNA-mediated knockdown or pharmacological inactivation (e.g. lidocaine, ropivacaine). As it remains unknown whether dysregulated VGSC expression in oncogenic cells enhances proliferative/metastatic potential by stimulating oncogenic signaling pathways, suppressing inhibitory pathways, or a combination of both, the focus of this study was to determine the status of signal transduction pathways following ion channel activation and/or inhibition. We hypothesized that upregulated VGSC expression enhances proliferative ability by stimulating oncogenic pathways and suppressing inhibitory pathways. By pharmacological activation of the over-expressed VGSCs in SW620 and SW480 human colon cancer cell lines, we concluded that VGSC activation resulted in both stimulative oncogenic signaling and suppressed inhibitory signaling, which were more consistently observed in the SW620 cell line vs SW480 cell line and more noticeable at 48h post-treatment vs 24h post-treatment.