Brief Article
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World J Gastroenterol. Dec 21, 2012; 18(47): 7087-7092
Published online Dec 21, 2012. doi: 10.3748/wjg.v18.i47.7087
Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice
Gui-Jun Zhao, Li-Xia Xu, Eagle SH Chu, Ning Zhang, Jia-Yun Shen, Alatangaole Damirin, Xiao-Xing Li
Gui-Jun Zhao, Alatangaole Damirin, College of Life Sciences, Inner Mongolia University, Hohhot 010021, Inner Mongolia Autonomous Region, China
Gui-Jun Zhao, Department of Gastroenterology and Hepatology, Inner Mongolia People’s Hospital, Hohhot 010017, Inner Mongolia Autonomous Region, China
Li-Xia Xu, Eagle SH Chu, Jia-Yun Shen, Xiao-Xing Li, Institute of Digestive Disease, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Hong Kong, China
Li-Xia Xu, Xiao-Xing Li, Shenzhen Research Institute, the Chinese University of Hong Kong, Shenzhen 518057, Guangdong Province, China
Ning Zhang, Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Zhao GJ performed the majority of experiments, provided financial support for this work and wrote the manuscript; Xu LX, Chu ESH, Zhang N and Shen JY provided vital reagents and analytical tools and performed the experiments; Damirin A designed the study; Li XX designed the study, provided part of the financial support and was also involved in revising the manuscript.
Supported by National Natural Science Foundation of China, No. 81201963; Inner Mongolia Natural Science Foundation of China, No. 2010MS1123
Correspondence to: Xiao-Xing Li, PhD, Institute of Digestive Disease, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong, Hong Kong, China. lxxstar@cuhk.edu.hk
Telephone: +852-37636108 Fax: +852-21445330
Received: September 11, 2012
Revised: December 4, 2012
Accepted: December 15, 2012
Published online: December 21, 2012
Processing time: 321 Days and 21.6 Hours
Abstract

AIM: To improve the outcome of orthotopic transplantation in a mouse model, we used an absorbable gelatin sponge (AGS) in nude mice to establish an orthotopic implantation tumor model.

METHODS: MHCC-97L hepatocellular carcinoma (HCC) cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice. One week later, the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice. The AGS was used to establish the nude mouse orthotopic implantation tumor model. The tumor suppressor gene, paired box gene 5 (PAX5), which is a tumor suppressor in HCC, was transfected into HCC cells to validate the model. Tumor growth was measured by bioluminescence imaging technology. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.

RESULTS: We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS. The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS. The detection of fluorescent signals showed that tumors grew in all live nude mice. The mice were divided into 3 groups: AGS-, AGS+/PAX5- and AGS+/PAX5+. Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice (P < 0.0001). These fluorescent signal results were consistent with observations made during surgery. Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC. Results from RT-PCR proved that the HCC originated from MHCC-97L cells.

CONCLUSION: Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.

Keywords: Hepatocellular carcinoma; Orthotopic transplantation tumor model; Absorbable gelatin sponge; Nude mice; Bioluminescence imaging