Aspirin inhibits hepatocellular carcinoma cell proliferation in vitro and in vivo via inducing cell cycle arrest and apoptosis.

Content Provider	Europe PMC
Author	Shi, Tingting Fujita, Koji Gong, Jian Nakahara, Mai Iwama, Hisakazu Liu, Shi Yoneyama, Hirohito Morishita, Asahiro Nomura, Takako Tani, Joji Takuma, Kei Tadokoro, Tomoko Himoto, Takashi Oura, Kyoko Tsutsui, Kunihiko Kobara, Hideki Masaki, Tsutomu
Copyright Year	2020
Abstract	Aspirin, a nonsteroidal anti-inflammatory drug (NSAID), is known to inhibit cell proliferation in a variety of cancers. However, the underlying mechanism of this inhibition remains unknown. We investigated the effects of aspirin on hepatocellular carcinoma (HCC) cells using in vitro and in vivo models. Six HCC cell lines and a liver cancer cell line including Huh-7 were used in assays that evaluated cell proliferation, cell cycle, and apoptosis. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), western blot analysis, and phosphorylated receptor tyrosine kinase array were used to evaluate the effects of aspirin on the cells, and microRNAs (miRNAs) were analyzed by a miRNA array chip. The results were validated in vivo using a nude mouse model of Huh-7-xenografted tumors. Our results showed that aspirin exhibited an antiproliferative effect on all cell lines. Moreover, aspirin induced G0/G1 cell cycle arrest and modulated the levels of cell cycle-related molecules such as cyclin E, cyclin D1, and cyclin-dependent kinase 2 (Cdk2). In addition, aspirin upregulated the levels of caspase-cleaved cytokeratin 18, increased the proportion of early apoptotic cells, decreased the levels of clusterin and heat shock protein 70 (HSP 70), upregulated the levels of miRNA-137 and inhibited epidermal growth factor receptor (EGFR) activation. In addition, we observed that aspirin suppressed cell proliferation partially through the miRNA-137/EGFR pathway. Our in vivo results showed that aspirin reduced the growth of xenograft tumors in nude mice. In conclusion, aspirin was able to inhibit the growth of HCC cells by cell cycle arrest, apoptosis, and alteration of miRNA levels in in vitro and in vivo models.
ISSN	1021335X
Journal	Oncology Reports
Volume Number	44
PubMed Central reference number	PMC7336451
Issue Number	2
PubMed reference number	32627038
e-ISSN	17912431
DOI	10.3892/or.2020.7630
Language	English
Publisher	D.A. Spandidos
Publisher Date	2020-05-29
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Shi et al.
Subject Keyword	hepatocellular carcinoma aspirin microRNA cell cycle apoptosis
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology