Abstract 6967: Suppression of protein X-mediated survivin expression enhance the antitumor effect of irinotecan in colorectal cancer

Abstract Survivin, an inhibitor of apoptosis protein, contributes to cancer drug resistance. This study investigated survivin's role in irinotecan resistance in colorectal cancer. RT-PCR and western blotting confirmed increased survivin expression in irinotecan-treated colorectal cancer cells. Knockdown of survivin by using siRNA decreased cell viability, confirming its anti-apoptotic function. Screening potential upstream regulators revealed ‘protein X’ but not ‘protein Y’, as a key mediator of survivin expression. ‘Protein X’ is overexpressed in many cancers and associated with drug resistance. We hypothesized that inhibiting ‘protein X’ could enhance irinotecan's effectiveness. Both genetic inhibition by siRNA and pharmacological inhibition with an ‘protein X’ inhibitor enhanced apoptotic effects of irinotecan in colorectal cancer cell lines. The synergistic effect was particularly pronounced in HCT116 cells, which showed the highest sensitivity to irinotecan. These findings suggest that targeting ‘protein X’-mediated survivin expression may be a promising strategy to overcome irinotecan resistance in colorectal cancer. This approach provides a novel perspective on enhancing the efficacy of irinotecan-based therapies and potentially improving outcomes for colorectal cancer patients. Further in vivo studies and clinical trials are warranted to validate these findings and explore the therapeutic potential of this combination approach. Citation Format: Se Yong Park, Ju-Hee Kang, Jung Ho Hwang, Sun-Ju Lee, Jun-Won Yun, Seung Hyun Oh. Suppression of protein X-mediated survivin expression enhance the antitumor effect of irinotecan in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6967.