Adipose tissue-derived mesenchymal stem cells suppress growth of Huh7 hepatocellular carcinoma cells via interferon (IFN)-β-mediated JAK/STAT1 pathway in vitro

Chun Sung Byun, Soonjae Hwang, Sung Hun Woo, Moon Young Kim, Jin Suk Lee, Jong In Lee, Jee Hyun Kong, Keum Seok Bae, Il Hwan Park, Sung Hoon Kim, Young Woo Eom

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Abstract

Interferon (IFN)-β and/or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) secreted by adipose tissue-derived mesenchymal stem cells (ASCs) have been proposed as key mechanistic factors in anti-cancer efficacy in lung cancer and breast cancer cells, where they act through paracrine signaling. We hypothesized that IFN-β and TRAIL produced by ASCs suppress proliferation of hepatocellular carcinoma cells (HCCs). The present study evaluated the anti-cancer effects of ASCs on HCCs in vitro. We found that indirect co-culture with ASCs diminished growth of Huh7 hepatocellular carcinoma cells with increased protein levels of p53/p21 and phosphorylated STAT1 (pSTAT1), without apoptosis. Treatment with ASC-conditioned medium (ASC-CM) also decreased growth of Huh7 cells through elevated p53/p21 and pSTAT1 signaling. ASC-CM-mediated inhibition of cell growth was neutralized in Huh7 cells treated with anti-IFN-β antibody compared to that in ASC-CM-treated Huh7 cells incubated with an anti-TRAIL antibody. Treatment with JAK1/JAK2 inhibitors recovered inhibition of growth in Huh7 cells incubated in ASC-CM or IFN-β via down-regulation of pSTAT1/p53/p21. However, treatment of IFN-β resulted in no alterations in resistance of Huh7 cells to TRAIL. Our findings suggest that ASCs decrease growth through activated STAT1-mediated p53/p21 by IFN-β, but not TRAIL, in Huh7 cells.

Original languageEnglish
Pages (from-to)609-619
Number of pages11
JournalInternational Journal of Medical Sciences
Volume17
Issue number5
DOIs
Publication statusPublished - 2020

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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