Abstract 6965: Atypical protein kinase C-ι inhibitor suppresses the proliferation of malignant pancreatic ductal adenocarcinoma cells

Abstract Pancreatic cancer is considered to be one of the most lethal malignant cancers as its diagnosis remains elusive if the disease progresses to an advanced stage. Moreover, pancreatic cancer is the third leading cause of cancer-related deaths in the U.S. Chemoresistance to various drugs for pancreatic cancer is the main reason for its aggressive nature. Atypical protein kinase is the family of protein kinases that contain two isoforms -ι and -ζ. These protein kinases which play a significant role in the signaling pathways have been proven to be involved in cancer cell proliferation and metastasis. (5-amino-1-((1R, 2S, 3S, 4R)-2, 3-dihydroxy-4-methyl cyclopentyl)-1H-imidazole-4-carboxamide-(ICA-1S), one of the specific inhibitors of Protein Kinase C-ι has been reported to inhibit the function of PKC-ι resulting to a decreased cell proliferation, decreased metastasis, and increased apoptosis. Our study focuses on using ICA-1S to inhibit PKC-ι in two pancreatic adenocarcinoma cell lines: ASPC1 and PANC1. Firstly, 50, 000 cells were seeded into 6 well plates and treated with different concentrations of ICA-1S (0.5µM, 5µM, 10µM, 20µM, and 50µM) in every 24 hours for three days. The drug-treated cells and the control were trypsinized to count the number of cells using Cellometer cell counting chambers. The highest percentage of inhibition by ICA-1S was observed at 10 µM for both the cell lines ASPC1 and PANC1 where the proliferation was observed to decrease at 52% in the case of ASPC1 and 49.8% in the case of PANC1 respectively. ICA-1S concentration of 10 µM is now used for further experiments. Western Blot analysis of both ASPC1 and PANC1 cell lines demonstrated the downregulation of the PKC-ι and PKC-ζ proteins. Similarly, the downregulation of apoptosis-related marker, Caspase 3 led us to hypothesize that apoptosis is induced in the drug-treated pancreatic cancer cells compared to the control. Mutation in KRAS is most common in pancreatic cancer where very few drugs have been approved by the FDA for the treatment of pancreatic adenocarcinoma. Thus, we will on the KRAS regulated pathway for further analysis. Further investigations would include the study of aPKC inhibitor-affected pathways using techniques like WST, immunoprecipitation assay, immunofluorescence, and Western blotting. Citation Format: Shreejana Rimal, Mildred Acevedo Duncan. Atypical protein kinase C-ι inhibitor suppresses the proliferation of malignant pancreatic ductal adenocarcinoma cells [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 6965.