Abstract PO-227: Role of IL-1β pathway in colon cancer progression and its therapeutic implications in African American colon cancer cell lines

Abstract

Abstract Background: Colorectal cancer (CRC) is the third most common cancer and third cause of cancer-related death among African Americans (AA) in the US. When compared to Caucasian Americans (CA), AA patients present with higher incidence and mortality rates for CRC. Recent findings indicate that they have reduced response to the standard of care chemotherapeutic agent 5-Fluorouracil (5-FU) as well as lower frequency of MSI tumors, making them also less likely to respond to conventional immunotherapies. Previous results from human genomic analyses suggest that certain differences seen in AA patients might be due to a decreased antitumor immune response as well as an increased expression of genes involved in inflammatory processes, such as Interleukin-1β (IL-1β). Therefore, we aimed to investigate the role of IL-1β in promoting cell proliferation, cell migration, 5-FU resistance and activation of specific inflammatory pathways in novel AA colon cancer cell lines, and how these responses would compare to well established CA colon cancer cell lines. Methods: Our approach includes using MTS colorimetric assay and Transwell assay to examine the effects of IL-1β treatment on cell proliferation and migration. We performed Western Blot analysis to detect expression of phosphoproteins following treatment with IL-1β. We also investigated how IL-1β affects 5-FU resistance in AA and CA colon cancer cell lines in terms of cell viability. Finally, we tested the ability of IL-1 Receptor antagonist (IL-1Ra) to inhibit the effects of IL-1β on cell proliferation, protein expression, and 5-FU response. Results: Our MTS assay results indicated that cell proliferation in response to IL-1β differs between the AA and the CA colon cancer cell lines, with the AA colon cancer cells being more responsive. Whereas, the migration rate is increased after stimulation with IL-1β for both AA and CA colon cancer cell lines. Protein expression of Phospho-IkB-alpha is increased in AA but not CA colon cancer cell lines following IL-1β treatment, while Phospho-JNK expression was different between the cell lines following treatment. Importantly, our results show that 5-FU efficacy is decreased in the presence of IL-1β for both AA and CA colon cancer cell lines and that treating the cells with IL-1Ra appeared to reestablish 5-FU cell killing effect. IL-1Ra also suppresses the effects of IL-1β on cell proliferation and protein expression. Conclusions: Taken together, our results demonstrated a differential response to IL-1β for the AA colon cancer cell lines, suggesting a probable role played by the cytokine in driving inflammation-related cancer progression and reveals a possible new target to exploit in immunotherapy for this population. Citation Format: Marzia Spagnardi, Jenny Paredes, Jone Garai, Jovanny Zabaleta, Jennie Williams, Laura Martello-Rooney. Role of IL-1β pathway in colon cancer progression and its therapeutic implications in African American colon cancer cell lines [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-227.