Abstract 6015: Effect of antineoplastic drugs on cell-to-cell communication in the progression of colorectal cancer

Abstract

Abstract Background: In the past few years, there has been notable progress in colorectal cancer research, resulting in novel development and delivery of drugs specifically designed for individual patient requirements. However, one of the major roadblocks in designing and treating colorectal cancer is the drug resistance found in advanced stages. Thus, there is a profound need to establish new methods to overcome this barrier. Previous work illustrated that cell-to-cell communications are dysfunctional for multitude of reasons in colorectal cancer cells. Restoration of cell-to-cell communication is a mean to deliver antineoplastic drugs via bystanding effect. Prior research has demonstrated that restoring gap junctions of cell-to-cell communication in breast cancer cells enhances the efficacy of cisplatin, a drug previously deemed resistant. Hence, this study seeks to assess the potency and efficacy of antineoplastic agents known to show resistance in colorectal cancer, with the intention to investigate how gap junctions can increase the efficacy of antineoplastic agents via restoration of cell-to-cell communication. Method: We assessed cell viability utilizing the RealTime Glo MT Cell Viability assay (Promega, Inc.). Four specific colorectal cancer cell lines, Caco2, HT-29, SW620, and SW480, were used. Four antineoplastic agents, doxorubicin, cediranib, nilotinib, and erlotinib, were selected for the study and subsequently in the combination study of gap junction enhancer. The lethal dose at 50% (LD50) was calculated for each antineoplastic agent in each cell line. Results: The results show significant variation of LD50. HT-29 cells dosed with doxorubicin showed LD50 of 8.9 µM, 1.6 µM, and 0.5 µM at 24 hours, 36 hours, and 48 hours of exposure, respectively. HT-29 cells dosed with erlotinib showed LD50 of 15.8 µM and 8.9 µM at 48 hours and 60 hours of exposure, respectively. SW620 dosed with doxorubicin showed LD50 is 0.5 µM at 36 hours of exposure. SW620 dosed with erlotinib showed LD50 of 15.8 µM and 0.5 µM at 48 hours and 60 hours of exposure, respectively. Caco2 cells dosed with cediranib showed LD50 of 2.8 µM and 1.6 µM at 36 hours and 48 hours of exposure, respectively. Conclusion: The findings from this study revealed varying LD50 values for these cell lines when treated with the four distinct drugs. This enabled us to determine a foundational effect of these drugs on these cell lines, which had not been previously identified. Discovering this foundational effect will allow us to investigate the synergy effect when combined with gap junction enhancer by setting a baseline effect using these results. Citation Format: Tomas Lugo, Annelise Nguyen. Effect of antineoplastic drugs on cell-to-cell communication in the progression of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6015.