Antitumor Effect of Low-Dose of Rapamycin in a Transgenic Mouse Model of Liver Cancer
- Author:
Hyung Soon LEE
1
;
Joon Ye KIM
;
Simon Weonsang RO
;
Myoung Soo KIM
;
Haeryoung KIM
;
Dong Jin JOO
Author Information
- Publication Type:Original Article
- From:The Korean Journal of Gastroenterology 2022;63(11):1007-1015
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:We investigate whether low-dose rapamycin is effective in preventing hepatocellular carcinoma (HCC) growth and treating HCC after tumor development in transgenic mice.
Materials and Methods:We established transgenic mice with HCC induced by activated HrasG12V and p53 suppression. Transgenic mice were randomly assigned to five experimental groups: negative control, positive control, tacrolimus only, rapamycin only, and tacrolimus plus rapamycin. The mice were further divided into two groups according to time to commencement of immunosuppressant treatment: de novo treatment and post-tumor development.
Results:In the de novo treatment group, marked suppression of tumor growth was observed in the rapamycin only group. In the post-tumor development group, the rapamycin only group displayed no significant suppression of tumor growth, compared to the positive control group. In T lymphocyte subset analysis, the numbers of CD4+ effector T cells and CD4+ regulatory T cells were significantly lower in the positive control, tacrolimus only, and tacrolimus plus rapamycin groups than the negative control group.Immunohistochemical analysis revealed significantly higher expression of phosphorylated-mTOR, 4E-BP1, and S6K1 in the positive control group than in the rapamycin only group.
Conclusion:Low-dose rapamycin might be effective to prevent HCC growth, but may be ineffective as a treatment option after HCC development.
