Establishment of an insufficient radiofrequency ablation orthotopic nude mouse model of hepatocellular carcinoma to study the invasiveness and metastatic potential of residual cancer

Zhang,Ning; Zhu,Hua; Dong,Ye‑Hao; Wang,Lu

doi:10.3892/ol.2019.10552

Establishment of an insufficient radiofrequency ablation orthotopic nude mouse model of hepatocellular carcinoma to study the invasiveness and metastatic potential of residual cancer

Authors:
- Ning Zhang
- Hua Zhu
- Ye‑Hao Dong
- Lu Wang
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Affiliations: Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China, Department of Oncology, The First People's Hospital of Jining, Jining, Shandong 272000, P.R. China, Reproductive Medicine Center, The Affiliated Hospital of Jining Medical College, Jining, Shandong 272000, P.R. China
Published online on: July 2, 2019 https://doi.org/10.3892/ol.2019.10552
Pages: 2548-2553

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Abstract

In order to assess the metastatic potential of residual hepatocellular carcinoma (HCC) following insufficient radiofrequency ablation (RFA) and to improve the current animal model, an insufficient RFA orthotopic nude mouse model of HCC was developed in the present study. A human HCC orthotopic nude mouse model was established using HCCLM3 cells, which has a high metastatic potential, labeled with green fluorescent protein. A total of 12 nude mice within the RFA group received insufficient RFA and 12 mice in the control group received RFA needle electrode puncture of the tumor without ablation, 3 weeks after implantation. To investigate tumor growth and metastasis, 4 weeks after RFA, six mice in each group were sacrificed and the remaining mice in each group were maintained until death to evaluate their life span. No mice died following insufficient RFA and the success rate was 100%. Compared with the control group, the intrahepatic and lung metastasis rates were higher in the RFA group, despite the mice having smaller tumor volumes and longer survival times. Lung and intrahepatic metastasis rates in the insufficient RFA group were 100% (6/6) and 66.67% (4/6), respectively, compared with 33.33% (2/6) and 0% (0/6), respectively, in the control group. As part of the study, a safe and reliable method to establish an insufficient RFA orthotopic nude mouse model was developed. The present study revealed that residual cancer following insufficient RFA had exhibited increased invasiveness and metastatic potential.

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1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Dutta R and Mahato RI: Recent advances in hepatocellular carcinoma therapy. Pharmacol Ther. 173:106–117. 2017. View Article : Google Scholar : PubMed/NCBI
3	Kawaguchi Y, Honda G, Endo I, Cherqui D and Kokudo N: Current technical issues for surgery of primary liver cancer. Liver Cancer. 6:51–58. 2016. View Article : Google Scholar : PubMed/NCBI
4	Lau WY and Lai EC: The current role of radiofrequency ablation in the management of hepatocellular carcinoma: A systematic review. Ann Surg. 249:20–25. 2009. View Article : Google Scholar : PubMed/NCBI
5	Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Nakagawa H, Asaoka Y, Sato T, Masuzaki R, Kondo Y, et al: Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol. 107:569–578. 2012. View Article : Google Scholar : PubMed/NCBI
6	Feng K, Yan J, Li X, Xia F, Ma K, Wang S, Bie P and Dong J: A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 57:794–802. 2012. View Article : Google Scholar : PubMed/NCBI
7	Park W, Chung YH, Kim JA, Jin YJ, Lee D, Shim JH, Lee D, Kim KM, Lim YS, Lee HC, et al: Recurrences of hepatocellular carcinoma following complete remission by transarterial chemoembolization or radiofrequency therapy: Focused on the recurrence patterns. Hepatol Res. 43:1304–1312. 2013. View Article : Google Scholar : PubMed/NCBI
8	Lam VW, Ng KK, Chok KS, Cheung TT, Yuen J, Tung H, Tso WK, Fan ST and Poon RT: Incomplete ablation after radiofrequency ablation of hepatocellular carcinoma: Analysis of risk factors and prognostic factors. Ann Surg Oncol. 15:782–790. 2008. View Article : Google Scholar : PubMed/NCBI
9	Zhang L, Yin X, Gan YH, Zhang BH, Zhang JB, Chen Y, Xie XY, Ge NL, Wang YH, Ye SL and Ren ZG: Radiofrequency ablation following first-line transarterial chemoembolization for patients with unresectable hepatocellular carcinoma beyond the Milan criteria. BMC Gastroenterol. 14:112014. View Article : Google Scholar : PubMed/NCBI
10	Yang BW, Liang Y, Xia JL, Sun HC, Wang L, Zhang JB, Tang ZY, Liu KD, Chen J, Xue Q, et al: Biological characteristics of fluorescent protein-expressing human hepatocellular carcinoma xenograft model in nude mice. Eur J Gastroenterol Hepatol. 20:1077–1084. 2008. View Article : Google Scholar : PubMed/NCBI
11	Wang L, Tang ZY, Qin LX, Wu XF, Sun HC, Xue Q and Ye SL: High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology. 32:43–48. 2000. View Article : Google Scholar : PubMed/NCBI
12	Sun FX, Tang ZY, Lui KD, Ye SL, Xue Q, Gao DM and Ma ZC: Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer. 66:239–243. 1996. View Article : Google Scholar : PubMed/NCBI
13	Bu W, Tang ZY, Sun FX, Ye SL, Liu KD, Xue Q, Chen J and Gao DM: Effects of matrix metalloproteinase inhibitor BB-94 on liver cancer growth and metastasis in a patient-like orthotopic model LCI-D20. Hepatogastroenterology. 45:1056–1061. 1998.PubMed/NCBI
14	Kong J, Kong L, Kong J, Ke S, Gao J, Ding X, Zheng L, Sun H and Sun W: After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma. J Transl Med. 10:2302012. View Article : Google Scholar : PubMed/NCBI
15	Xu M, Xie XH, Xie XY, Xu ZF, Liu GJ, Zheng YL, Huang GL, Wang W, Zheng SG and Lü MD: Sorafenib suppresses the rapid progress of hepatocellular carcinoma after insufficient radiofrequency ablation therapy: An experiment in vivo. Acta Radiol. 54:199–204. 2013. View Article : Google Scholar : PubMed/NCBI
16	Ke S, Ding XM, Kong J, Gao J, Wang SH, Cheng Y and Sun WB: Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma. J Transl Med. 8:732010. View Article : Google Scholar : PubMed/NCBI
17	Nakagawa H, Mizukoshi E, Iida N, Terashima T, Kitahara M, Marukawa Y, Kitamura K, Nakamoto Y, Hiroishi K, Imawari M and Kaneko S: In vivo immunological antitumor effect of OK-432-stimulated dendritic cell transfer after radiofrequency ablation. Cancer Immunol Immunother. 63:347–356. 2014. View Article : Google Scholar : PubMed/NCBI
18	Massazza G, Tomasoni A, Lucchini V, Allavena P, Erba E, Colombo N, Mantovani A, D'Incalci M, Mangioni C and Giavazzi R: Intraperitoneal and subcutaneous xenografts of human ovarian carcinoma in nude mice and their potential in experimental therapy. Int J Cancer. 44:494–500. 1989. View Article : Google Scholar : PubMed/NCBI
19	Niederberger M, DeLozier-Blanchet CD, Hedinger CE and Walt H: Differences between subcutaneous and intraperitoneal forms of three human testicular teratocarcinomas in nude mice. Cancer. 61:1571–1578. 1988. View Article : Google Scholar : PubMed/NCBI
20	Kasugai H, Osaki Y, Oka H, Kudo M and Seki T; Osaka Liver Cancer Study Group, : Severe complications of radiofrequency ablation therapy for hepatocellular carcinoma: An analysis of 3,891 ablations in 2,614 patients. Oncology. 72 (Suppl 1):S72–S75. 2007. View Article : Google Scholar
21	Koda M, Murawaki Y, Hirooka Y, Kitamoto M, Ono M, Sakaeda H, Joko K, Sato S, Tamaki K, Yamasaki T, et al: Complications of radiofrequency ablation for hepatocellular carcinoma in a multicenter study: An analysis of 16 346 treated nodules in 13 283 patients. Hepatol Res. 42:1058–1064. 2012. View Article : Google Scholar : PubMed/NCBI
22	Kong J, Kong J, Pan B, Ke S, Dong S, Li X, Zhou A, Zheng L and Sun WB: Insufficient radiofrequency ablation promotes angiogenesis of residual hepatocellular carcinoma via HIF-1α/VEGFA. PLoS One. 7:e372662012. View Article : Google Scholar : PubMed/NCBI