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Human multi-drug resistant hepatocellular carcinoma induced in nude mice by B-ultrasonographically-directed orthotopic implantation: a new experimental model |
Lei Ding, Xiao-Ping Chen, Zhi-Wei Zhang, Kai Jing and Wan-Guang Zhang |
Wuhan, China
Author Affiliations: Hepatic Surgery Center, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China (Ding L, Chen XP, Zhang ZW, Jing K and Zhang WG); Department of Oncology Center, Beijing Shijitan Hospital, Beijing 100038, China (Ding L)
Corresponding Author: Lei Ding, MD, Department of Oncology Center, Beijing Shijitan Hospital, Beijing 100038, China (Tel: 86-10-83036259; Email: dinglei1005@yahoo.com.cn) |
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Abstract BACKGROUND: Present studies on the reversal of multi-drug resistance (MDR) are almost entirely limited to in vitro systems, and are seldom carried out in vivo. In order to study MDR under the in vivo situation, a MDR cell strain was used to establish a model in nude mice via orthotopic implantation directed by B-ultrasonography. This model is expected to provide a good platform for evaluating strategies to reverse the phenomenon of primary hepatocellular carcinoma (HCC) MDR.
METHODS: An orthotopic MDR1 hepatoma was obtained by injecting the cell lines HepG2 and HepG2/ADM subserosally into the liver of nude mice (10 control and 20 MDR mice). The injections were made under B-ultrasonographic direction. Ultrasonography and laparotomy were used to assess tumor growth, and the long chain PCR technique was applied to sequence the MDR1 gene from multi-drug resistant human HCC cells, HepG2/ADM, and corresponding implanted tumor tissues. Furthermore, MDR1 mRNA and P-gp protein expression were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical methods.
RESULTS: The success rates of tumor implantation and induction of MDR were 100% (30/30) and 95% (19/20), respectively. The 3.8kbp MDR1 gene band was detected from the HepG2/ADM cell line and the corresponding implanted tumor tissues, and the MDR1 gene sequence coincided with that reported in GenBank. The expressions of MDR1 mRNA and P-gp protein in MDR mice were significantly higher than those in the control group. There was a significant difference in P-gp protein expression between MDR and control mice.
CONCLUSION: A MDR model has been successfully established in nude mice via orthotopic implantation of multi-drug resistant human HCC cells directed by ultrasonography.
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Cite this article: |
Ding L,
Chen XP,
Zhang ZW,
et al.
Human multi-drug resistant hepatocellular carcinoma induced in nude mice by B-ultrasonographically-directed orthotopic implantation: a new experimental model.
Hepatobiliary Pancreat Dis Int
2007;
6(4):
393-398. DOI:
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URL: |
http://dx.doi.org/ OR http://www.hbpdint.com/EN/Y2007/V6/I4/393 |
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