The therapeutic effect of HSV1-hGM-CSF combined with doxorubicin on the mouse breast cancer model
10.3760/cma.j.issn.0253-3766.2018.03.004
- VernacularTitle: 携带重组人粒细胞巨噬细胞集落刺激因子的溶瘤性1型单纯疱疹病毒联合阿霉素治疗小鼠乳腺癌的效果
- Author:
Xiufen ZHUANG
1
;
Shuren ZHANG
2
;
Binlei LIU
3
;
Jiliang WU
4
;
Xiaoqin LI
1
;
Hangang GU
1
;
Yang SHU
5
Author Information
1. Department of Oncology, the Affiliated Hospital of Jiangsu University, Zhenjiang 212000, China
2. Department of Immunology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
3. Key Laboratory of Fermentation Engineer (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China
4. School of Pharmacology, Hubei University of Science and Technology, Xianning 437100, China
5. Department of Central Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, China
- Publication Type:Journal Article
- Keywords:
Oncolytic virus;
Breast neoplasms;
Herpes simplex virus, HSV;
Doxorubicin
- From:
Chinese Journal of Oncology
2018;40(3):178-185
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice.
Methods:We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 μg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed.
Results:Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro. Doxorubicin induced the G2/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm3, (216.80±57.18)mm3, (246.10±21.90)mm3, (327.50±44.24)mm3, (213.30±32.31)mm3 and (495.80±75.87)mm3 in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo (P<0.001). The median survival times were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above, respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM-CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control (P<0.05).
Conclusion:Synergistic effect of sequential treatment with doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.
