Expression of receptor interacting protein 1 and receptor interacting protein 3 oval cells in a rat model of hepatocarcinogenesis

Wójcik,Marta; Bobowiec,Ryszard; Lisiecka,Urszula; Śmiech,Anna

doi:10.3892/etm.2018.5988

Expression of receptor interacting protein 1 and receptor interacting protein 3 oval cells in a rat model of hepatocarcinogenesis

Authors:
- Marta Wójcik
- Ryszard Bobowiec
- Urszula Lisiecka
- Anna Śmiech
View Affiliations

Affiliations: Department of Pathophysiology, Faculty of Veterinary Medicine, University of Life Sciences, 20‑033 Lublin, Poland, Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences, 20‑033 Lublin, Poland, Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Life Sciences, 20‑033 Lublin, Poland
Published online on: March 22, 2018 https://doi.org/10.3892/etm.2018.5988
Pages: 4448-4456

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

When apoptosis is suppressed in a neoplastic state, necroptosis may enable an anticancer response. In the present study, the association between apoptosis and necroptosis was assessed in a partial hepatectomy (PH)/diethylnitrosamine (DEN) rat model of hepatocarcinogenesis. Isolated oval cells (OCs) were analysed at 24, 48 and 72 h and at the first and second week of incubation. Phenotypic studies, apoptosis and necroptosis detection and proliferative activity assays were also performed on the OCs. The OCs were isolated from non‑neoplastic (PH) and neoplastic (PH/DEN) livers, which expressed receptor interacting protein (RIP) 1 and RIP3. Western blot analysis revealed that the RIP1 and RIP3 expression in the PH/DEN OCs started to increase at 72 h and continually increased to the end of cell culture. Compared with the PH OCs, the cells isolated from PH/DEN rats exhibited significantly less potential for apoptosis (P<0.05). There were a minimal number of apoptotic PH/DEN OCs (2.82±1.1%) at 72 h. In addition, the PH/DEN OCs demonstrated progressive proliferative activity during incubation, which was significantly increased compared with the PH OCs at ≥72 h. The present study revealed that PH/DEN OCs, which trigger hepatic cancer, have a high proliferative activity and suppress apoptosis. It was also observed that, based on the expression of RIP3 and RIP1, necroptosis may be maintained and may serve as an alternative pathway for programmed PH/DEN OC death.

View Figures

View References

1	Schlageter M, Terracciano LM, D'Angelo S and Sorrentino P: Histopatholgy of hepatocellular carcinoma. World J Gastroenterol. 20:15955–15964. 2014. View Article : Google Scholar : PubMed/NCBI
2	Zou C, Zhang H, Li Q, Xiao H, Yu L, Ke S, Zhou L, Liu W, Wang W, Huang H, et al: Heme-oxygenase-1: A molecular brake on hepatocellular carcinoma cell migration. Carcinogenesis. 32:1840–1848. 2011. View Article : Google Scholar : PubMed/NCBI
3	Lee KP, Lee JH, Kim TS, Park HD, Byun JS, Kim MC, Jeong WI, Calvisi DF, Kim JM and Lim DS: The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA. 107:8248–8253. 2010. View Article : Google Scholar : PubMed/NCBI
4	Wójcik M, Bobowiec R and Martelli F: Effect of carotenoids on in vitro proliferation and differentiation of oval cells during neoplastic and non-neoplastic liver injures in rats. J Physiol Pharmacol. 59 Suppl 2:S203–S213. 2008.
5	Zheng T, Wang J, Jiang H and Liu L: Hippo signalling in oval cells and hepatocarcinogenesis. Cancer Lett. 302:91–99. 2011. View Article : Google Scholar : PubMed/NCBI
6	Jin J, Jin X, Qian C, Ruan Y and Jiang H: Signaling network of OSW-1-induced apoptosis and necroptosis in hepatocellular carcinoma. Mol Med Rep. 7:1646–1650. 2013. View Article : Google Scholar : PubMed/NCBI
7	Fulda S: The mechanism of necroptosis in normal and cancer cell. Cancer Biol Ther. 14:999–1004. 2013. View Article : Google Scholar : PubMed/NCBI
8	Jouan-Lanhouet S, Riquet F, Duprez L, Vanden Berhe T, Takahashi N and Vandenabeele P: Necroptosis, in vivo detection in experimental disease models. Semin Cell Devel Biol. 35:2–13. 2014. View Article : Google Scholar
9	Schattenberg JM, Schumann M and Galle PR: Cell death and hepatocarcinogenesis: Dysregulation of apoptosis signaling pathways. J Gastroenterol Hepatol. 26 Suppl 1:S213–S219. 2011. View Article : Google Scholar
10	Hu X, Han W and Li L: Targeting the weak point of cancer by induction of necroptosis. Autophagy. 3:490–492. 2007. View Article : Google Scholar : PubMed/NCBI
11	Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R and Gu W: Ferroptosis as a p53-mediated activity during tumor suppression. Nature. 520:57–62. 2015. View Article : Google Scholar : PubMed/NCBI
12	He S, Wang L, Miao L, Wang T, Du F, Zhao L and Wang X: Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 137:1100–1111. 2009. View Article : Google Scholar : PubMed/NCBI
13	Vandenabeele P, Galluzi L, Vanden Berghe T and Kroemer G: Molecular mechanisms of necroptosis: An ordered cellular explosion. Nat Rev Mol Cell Biol. 11:700–714. 2010. View Article : Google Scholar : PubMed/NCBI
14	Fulda S: Therapeutic exploitation of necroptosis for cancer therapy. Semin Cell Dev Biol. 35:51–56. 2014. View Article : Google Scholar : PubMed/NCBI
15	Saeed WK and Jun DW: Necroptosis: An emerging type of cell death in liver diseases. World J Gastroenterol. 20:12526–12532. 2014. View Article : Google Scholar : PubMed/NCBI
16	Solt D and Farber E: New principle for the analysis of chemical carcinogenesis. Narure. 263:701–703. 1976.
17	Higgins G and Anderson G: Experimental pathology of the liver restoration of the liver of the white rat following partial surgical removal. Arch Pathol (Chic). 12:186–202. 1931.
18	Shupe TD, Piscaglia AC, Oh SH, Gasbarrini A and Petersen BE: Isolation and characterization of hepatic stem cells, or ‘oval cells,’ from rat livers. Method Mol Biol. 482:387–405. 2009. View Article : Google Scholar
19	He ZP, Tan WQ, Tang YF, Zhang HJ and Feng MF: Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers. Cell Prolif. 37:177–187. 2004. View Article : Google Scholar : PubMed/NCBI
20	Strober W: Trypan blue exclusion test of cell viability. Curr Protoc Immunol. 21:3B:A.3B.1–A.3B.2. 2001.
21	Head KW, Cullen JM, Dubielzig RR, Else RW, Misdorp W, Patnaik AK, Tateyama S and Van Der Gaag I: Histological Classification of Tumors of the Alimentary System of Domestic AnimalsSecond Series. WHO, Armed Forces Institute of Pathology; Washington, DC: 2003
22	Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265–275. 1951.PubMed/NCBI
23	Wójcik M, Bobowiec R, Lisiecka U and Kostro K: Proliferation, differentiation and apoptosis of choline deficient ethionine supplemented diet-rat oval cells under the influence of 2-methoxyestradiol. J Physiol Pharmacol. 63:669–676. 2012.PubMed/NCBI
24	Wójcik M, Wessely-Szponder J and Kosior-Korzecka U: Proliferative and oxidative response of hepatocytes (Hep) and hepatic stellate cells (HSC) isolated from rats exposed to ketogenic diet. Pol J Vet Sci. 17:703–711. 2014. View Article : Google Scholar : PubMed/NCBI
25	Kearney CJ, Cullen SP, Clancy D and Martin SJ: RIPK1 can function as an inhibitor rather than an initiator of PIPK3-dependent necroptosis. FEBS J. 281:4921–4934. 2014. View Article : Google Scholar : PubMed/NCBI
26	Upton JW, Kaiser WJ and Mocarski ES: DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus VIRA. Cell Host Microbe. 15:290–297. 2012. View Article : Google Scholar
27	Christofferson DE and Yuan J: Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol. 22:263–268. 2010. View Article : Google Scholar : PubMed/NCBI
28	Declercq W, Vanden Berghe T and Vandenabeele P: RIP kinase at the crossroads of cell death and survival. Cell. 138:229–232. 2009. View Article : Google Scholar : PubMed/NCBI
29	Newton K: RIPK1 and RIPK3: Critical regulators of inflammation and cell death. Trends Cell Biol. 25:347–353. 2015. View Article : Google Scholar : PubMed/NCBI
30	Zhou W and Yuan J: Necroptosis in health and diseases. Semin Cell Dev Biol. 35:14–23. 2014. View Article : Google Scholar : PubMed/NCBI