Aspirin inhibits cholangiocarcinoma cell proliferation via cell cycle arrest in vitro and in vivo.

Abstract

Cholangiocarcinoma is the most common biliary duct malignancy and the second most common primary liver cancer, accounting for 10‑20% of hepatic malignancies. With high mortality and poor prognosis, the 5‑year 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 HuCCT‑1 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 cell‑cycle related proteins in cholangiocarcinoma cells (HuCCT‑1 cells) but did not induce apoptosis. The expression of miR‑340‑5p was significantly upregulated after treatment, and overexpression of miR‑340‑5p inhibited the proliferation of HuCCT‑1 cells and decreased the levels of cyclin D1. TKKK cells had low miR‑340‑5p 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 miR‑340‑5p/cyclin D1 axis.

• Authors: Tingting Shi, Jian Gong, Koji Fujita, Noriko Nishiyama, Hisakazu Iwama, Shi Liu, Mai Nakahara, Hirohito Yoneyama, Asahiro Morishita, Takako Nonura, Hideki Kobara, Keiichi Okano, Yasuyuki Suzuki, Tsutomu Masaki
• Journal: International journal of oncology (Int J Oncol) Vol. 58 Issue 2 Pg. 199-210 (02 2021) ISSN: 1791-2423 [Electronic] Greece
• PMID: 33491760 (Publication Type: Journal Article)

Chemical References

• CCND1 protein, human
• MIRN340 microRNA, human
• MicroRNAs
• Cyclin D1
• Aspirin

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Aspirin (pharmacology, therapeutic use)
• Bile Duct Neoplasms (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects, genetics)
• Cholangiocarcinoma (drug therapy, genetics, pathology)
• Computational Biology
• Cyclin D1 (genetics)
• Female
• G1 Phase Cell Cycle Checkpoints (drug effects, genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mice
• MicroRNAs (metabolism)
• Xenograft Model Antitumor Assays