IDENTIFICATION OF SB216763 AS A PROMISING TARGETED THERAPY FOR POOR-PROGNOSIS CHOLANGIOCARCINOMA PATIENTS

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the bile ducts. Its incidence is the highest and represents a major public health burden in Thailand. CCA patients generally exhibit poor prognosis due to late diagnosis and the lack of effective therapeutic options. Our previous bioinformatic analysis stratified CCA patients into two groups with distinct survival outcomes and classified CCA cell lines into two groups representing the distinct patient groups. To identify a promising therapeutic strategy for CCA patients, particularly those with poor prognosis, we integrated bioinformatic and experimental approaches. In this study, SB216763, a GSK3β inhibitor, was identified as a promising targeted therapeutic candidate for CCA patients with poorer prognosis. RT-qPCR and Western blot analyses revealed that GSK3β was upregulated in RMCCA-1 cells, representing CCA with poor-prognosis group, compared to CCLP-1 cells, representing CCA with better-prognosis group. SB216763 treatment activated β-catenin, confirming GSK3β inhibition. MTT assays demonstrated that RMCCA-1 cells were more sensitive to SB216763 treatment than CCLP-1 cells. Microscopic observations also supported this differential response. Collectively, our study highlights GSK3β inhibition by SB216763 as a potential precision medicine strategy for CCA patients with poor prognosis, underscoring the importance of patient group stratification in guiding personalized therapeutic approaches.