Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma in vitro

Kim,Jong  Bin; Lee,Seulki; Kim,Hye  Ri; Park,Seo‑Young; Lee,Minjong; Yoon,Jung‑Hwan; Kim,Yoon  Jun

doi:10.3892/ol.2018.8441

Transforming growth factor‑β decreases side population cells in hepatocellular carcinoma in vitro

Authors:
- Jong Bin Kim
- Seulki Lee
- Hye Ri Kim
- Seo‑Young Park
- Minjong Lee
- Jung‑Hwan Yoon
- Yoon Jun Kim
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Affiliations: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Jongno, Seoul 110‑799, Republic of Korea, Biomedical Research Institute, Seoul National University Hospital, Jongno, Seoul 110‑799, Republic of Korea
Published online on: April 5, 2018 https://doi.org/10.3892/ol.2018.8441
Pages: 8723-8728

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Abstract

Hepatocellular carcinoma (HCC) can result from hepatitis B or C infection, fibrosis or cirrhosis. Transforming growth factor‑β (TGF‑β) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role is controversial in hepatocarcinogenesis. In the present study, the effect of TGF‑β on the HCC Huh‑7 and Huh‑Bat cell lines was evaluated. To study the effect of TGF‑β, Huh‑7 and Huh‑Bat cells were treated with TGF‑β and a TGF‑β receptor inhibitor (SB431542). Cell survival, cell cycle, numbers of side population (SP) cells and expression of the cancer stem cell marker cluster of differentiation (CD)133, epithelial‑mesenchymal transition markers (E‑cadherin, α‑smooth muscle actin and vimentin) and TGF‑β‑regulated proteins [phospho‑c‑Jun N‑terminal kinase (p‑JNK), p‑c‑Jun and p‑smad2] were investigated. TGF‑β treatment resulted in decreased cell survival with a targeted effect on SP cells. Expression of CD133 and vimentin was upregulated by treatment with the TGF‑β receptor antagonist SB431542, but not with TGF‑β. By contrast, TGF‑β induced accumulation of cells at G0/G1, and upregulated expression of p‑JNK, p‑c‑Jun and p‑smad2. However, these effects were blocked when cells were treated with TGF‑β plus SB431542, indicating the specificity of the TGF‑β effect. The present results indicated that TGF‑β has anticancer effects mediated by survival inhibition of cancer stem cells, which may be developed as a novel therapy for HCC.

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