Interferon-λ1 induces G1 phase cell cycle arrest and apoptosis in gastric carcinoma cells in vitro

Gao,Zhitao; Zhu,Moli; Wu,Yaping; Gao,Pan; Qin,Zhihai; Wang,Hui

doi:10.3892/or.2014.3185

Interferon-λ1 induces G1 phase cell cycle arrest and apoptosis in gastric carcinoma cells in vitro

Authors:
- Zhitao Gao
- Moli Zhu
- Yaping Wu
- Pan Gao
- Zhihai Qin
- Hui Wang
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Affiliations: Research Center for Immunology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
Published online on: May 15, 2014 https://doi.org/10.3892/or.2014.3185
Pages: 199-204

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Abstract

The aim of the present study was to examine the potential antitumor action of IFN-λ1 in human gastric carcinoma cell lines and the possible interaction between IFN-λ1 and human gastric carcinoma cells. Gastric carcinoma HGC-27 and SGC-7901 cells were treated with IFN-λ1 (0, 10, 100, 1000 ng/ml) for 48 h. Cytotoxicity was examined using an MTT method. Cell cycle distribution was examined using propidium iodide staining. Apoptosis was examined using the Annexin V-FITC/PI apoptosis kit. By using flow cytometry and JC-1 probe, the mitochondrial membrane potential of cells following treatment with IFN-λ1 was also examined. Expression levels of representative apoptosis‑related proteins were evaluated by western blot analysis. IFN-λ1 inhibited the proliferation of gastric carcinoma cells in a concentration‑dependent manner. IFN-λ1 increased the accumulation of cells in the sub-G0 phase and arrested the cells in the G1 phase. Exposure to IFN‑λ1 decreased the mitochondrial membrane potential and increased apoptosis. Moreover, IFN‑λ1 exposure upregulated the expression of p21, p27 and Bax, downregulated the expression of Bcl‑2, increased the release of cytochrome c and apoptosis-inducing factor (AIF) and activated caspase-3 and caspase-9. In conclusion, IFN-λ1 inhibits the proliferation of gastric carcinoma cells by arresting the cells in the G1 phase and by inducing mitochondrial‑mediated apoptosis.

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1	Lopušná K, Režuchová I, Betáková T, et al: Interferons lambda, new cytokines with antiviral activity. Acta Virol. 57:171–179. 2013.PubMed/NCBI
2	Tagawa M, Kawamura K, Li Q, et al: A possible anticancer agent, type III interferon, activates cell death pathways and produces antitumor effects. Clin Dev Immunol. 2011:4790132011. View Article : Google Scholar : PubMed/NCBI
3	Li Q, Kawamura K, Okamoto S, et al: Adenoviruses-mediated transduction of human oesophageal carcinoma cells with the interferon-λ genes produced anti-tumour effects. Br J Cancer. 105:1302–1312. 2011.PubMed/NCBI
4	Donnelly RP and Kotenko SV: Interferon-lambda: a new addition to an old family. J Interferon Cytokine Res. 30:555–564. 2010. View Article : Google Scholar : PubMed/NCBI
5	Tamura W and Fukami N: Early gastric cancer and dysplasia. Gastrointest Endosc Clin N Am. 23:77–94. 2013. View Article : Google Scholar : PubMed/NCBI
6	Hu Y, Fang JY and Xiao SD: Can the incidence of gastric cancer be reduced in the new century? J Dig Dis. 14:11–15. 2013. View Article : Google Scholar : PubMed/NCBI
7	Iravani O, Tay BW, Chua PJ, et al: Claudins and gastric carcinogenesis. Exp Biol Med. 238:344–349. 2013. View Article : Google Scholar : PubMed/NCBI
8	Saito H, Takaya S, Fukumoto Y, et al: Clinicopathologic characteristics and prognosis of gastric cancer in young patients. Yonago Acta Med. 55:57–61. 2012.PubMed/NCBI
9	Wongthida P, Diaz RM, Galivo F, et al: Type III IFN interleukin-28 mediates the antitumor efficacy of oncolytic virus VSV in immune-competent mouse models of cancer. Cancer Res. 70:4539–4549. 2010. View Article : Google Scholar : PubMed/NCBI
10	Yan Y, Zhang J, Liu Y, et al: Inhibition of lung adenocarcinoma transfected with interleukin 28A recombinant adenovirus (Ad- mIFN-λ2) in vivo. Cancer Biother Radiopharm. 28:124–130. 2013.PubMed/NCBI
11	Steen HC and Gamero AM: Interferon-lambda as a potential therapeutic agent in cancer treatment. J Interferon Cytokine Res. 30:597–602. 2010. View Article : Google Scholar : PubMed/NCBI
12	Ding F, Shao ZW, Yang SH, et al: Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells. Apoptosis. 17:579–590. 2012. View Article : Google Scholar : PubMed/NCBI
13	Mitrea DM, Yoon MK, Ou L, et al: Disorder-function relationships for the cell cycle regulatory proteins p21 and p27. Biol Chem. 393:259–274. 2012. View Article : Google Scholar : PubMed/NCBI
14	Wang L, Wang G, Yang D, et al: Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression. Mol Med Rep. 8:1279–1285. 2013.PubMed/NCBI
15	Zhang Z, Du GJ, Wang CZ, et al: Compound K, a ginsenoside metabolite, inhibits colon cancer growth via multiple pathways encluding p53-p21 interactions. Int J Mol Sci. 14:2980–2995. 2013. View Article : Google Scholar : PubMed/NCBI
16	Abushahba W, Balan M, Castaneda I, et al: Antitumor activity of type I and type III interferons in BNL hepatoma model. Cancer Immunol Immunother. 59:1059–1071. 2010. View Article : Google Scholar : PubMed/NCBI
17	Yang L, Wei J and He S: Integrative genomic analyses on interferon-lambdas and their roles in cancer prediction. Int J Mol Med. 25:299–304. 2010.PubMed/NCBI
18	Li Q, Kawamura K, Ma G, et al: Interferon-lambda induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents. Eur J Cancer. 46:180–190. 2010. View Article : Google Scholar : PubMed/NCBI
19	Lasfar A, Abushahba W, Balan M, et al: Interferon lambda: a new sword in cancer immunotherapy. Clin Dev Immunol. 2011:3495752011. View Article : Google Scholar : PubMed/NCBI
20	George PM, Badiger R, Alazawi W, et al: Pharmacology and therapeutic potential of interferons. Pharmacol Ther. 135:44–53. 2012. View Article : Google Scholar : PubMed/NCBI
21	Renault TT, Teijido O, Antonsson B, et al: Regulation of Bax mitochondrial localization by Bcl-2 and Bcl-x (L): keep your friends close but your enemies closer. Int J Biochem Cell Biol. 45:64–67. 2013. View Article : Google Scholar : PubMed/NCBI
22	Low IC, Kang J and Pervaiz S: Bcl-2: a prime regulator of mitochondrial redox metabolism in cancer cells. Antioxid Redox Signal. 15:2975–2987. 2011. View Article : Google Scholar : PubMed/NCBI
23	Shamas-Din A, Kale J, Leber B, et al: Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol. 5:a0087142013. View Article : Google Scholar : PubMed/NCBI
24	Imesch P, Scheiner D, Szabo E, et al: Conjugates of cytochrome c and antennapedia peptide activates apoptosis and inhibit proliferation of HeLa cancer cells. Exp Ther Med. 6:786–790. 2013.
25	Liang J, Yu Y, Wang B, et al: Ginsenoside Rb1 attenuates oxygen-glucose deprivation-induced apoptosis in SH-SY5Y cells via protection of mitochondria and inhibition of AIF and cytochrome c release. Molecules. 18:12777–12792. 2013. View Article : Google Scholar : PubMed/NCBI
26	Park C, Jeong NY, Kim GY, et al: Momilactone B induces apoptosis and G1 arrest of the cell cycle in human monocytic leukemia U937 cells through downregulation of pRB phosphorylation and induction of the cyclin-dependent kinase inhibitor p21Waf1/Cip1. Oncol Rep. 31:1653–1660. 2014.
27	Koyama M, Sowa Y, Hitomi T, et al: Perillyl alcohol causes G1 arrest through p15(INK4b) and p21(WAF1/Cip1) induction. Oncol Rep. 29:779–784. 2013.PubMed/NCBI