ABSTRACT
Cholangiocarcinoma is the most common biliary duct malignancy and the second most common primary liver cancer, accounting for 1020% of hepatic malignancies. With high mortality and poor prognosis, the 5year survival rate of cholangiocarcinoma is only 10%. A previous study demonstrated a significant association between aspirin use and a decreased risk of cholangiocarcinoma. However, the effect of aspirin on cholangiocarcinoma remains unknown. Therefore, the aim of the present study was to investigate the effects of aspirin on cholangiocarcinoma in vitro and in vivo. Three cholangiocarcinoma cell lines were used to analyze the effect of aspirin on cell proliferation, cell cycle progression, apoptosis, and the regulation of microRNAs. MicroRNAs are known to regulate the development and progression of various types of cancer. An HuCCT1 xenograft model was used for the in vivo study. It was determined that aspirin inhibited the proliferation of human cholangiocarcinoma cells (except TKKK cells). Aspirin induced cell cycle arrest in the G0/G1 phase and regulated cellcycle related proteins in cholangiocarcinoma cells (HuCCT1 cells) but did not induce apoptosis. The expression of miR3405p was significantly upregulated after treatment, and overexpression of miR3405p inhibited the proliferation of HuCCT1 cells and decreased the levels of cyclin D1. TKKK cells had low miR3405p expression, which may explain why aspirin had no effect on their proliferation. In vivo, aspirin reduced the growth of xenografted tumors. In conclusion, the present study indicated that aspirin partially inhibited cholangiocarcinoma cell proliferation and tumor growth by inducing G0/G1 phase cell cycle arrest, potentially through the miR3405p/cyclin D1 axis.
