Establishment and Characterization of Three Gemcitabine-Resistant Human Intrahepatic Cholangiocarcinoma Cell Lines

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. The results disclosed that GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as EMT, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species (ROS) might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches.