Abstract 719: Combination of atypical protein kinase-C inhibitor and 5-fluorouracil retards the proliferation of colorectal cancer cells

Abstract

Abstract Colorectal cancer (CRC) is the third most common malignancy and considered as the fourth most common cause of cancer-related death worldwide. Although the number of CRC survivors with stage II and III are increasing, more than 50% of patients are diagnosed with stage III or beyond where the distant disease progression has already occurred. Surgical removal of cancerous tissue coupled with chemotherapeutic intervention is the main treatment of metastatic CRC and only hope of enhanced survival. The treatment of metastatic CRC considered palliative for many years aiming for an improved life, with little hope of a cure, highlighting the need for developing novel targeted therapy for CRC. Dysregulation of kinases has been shown to be pivotal of the various pathological process including cancer. Human protein kinases constitute a complicated system with intricate internal and external interaction which stimulates various cellular processes such as cell growth, metabolism, survival, and apoptosis. In this study, a combination of atypical protein kinase c (aPKC) inhibitor (ICA-I, PKC-ι inhibitor or ζ-Stat, PKC-ζ inhibitor) and 5-FU was used to examine the effect of aPKC and thymidylate synthase on CRC cells viability. The cell lines tested were LoVo and RKO CRC cells. Our findings showed that the combination of aPKC inhibitor and 5-FU significantly reduced the viability and induce apoptosis of CRC cells. These data suggest that the simultaneous knockdown of upstream aPKC protein and downstream DNA replication would be a useful approach to combat CRC and to improve overall patients’ survival rate. These results indicate the possibility of utilizing aPKC as the potential therapeutic targets in addition to blocking DNA synthesis in metastatic CRC. Citation Format: S M Anisul Islam, Avijit Dey, Mildred Acevedo-Duncan. Combination of atypical protein kinase-C inhibitor and 5-fluorouracil retards the proliferation of colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 719.