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


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.

SUBMITTER: Shi T 

PROVIDER: S-EPMC7336451 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Shi Tingting T   Fujita Koji K   Gong Jian J   Nakahara Mai M   Iwama Hisakazu H   Liu Shi S   Yoneyama Hirohito H   Morishita Asahiro A   Nomura Takako T   Tani Joji J   Takuma Kei K   Tadokoro Tomoko T   Himoto Takashi T   Oura Kyoko K   Tsutsui Kunihiko K   Kobara Hideki H   Masaki Tsutomu T  

Oncology reports 20200529 2


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  ...[more]

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