| LIU Lin-lin,CHANG Xiao-min,ZHANG Qi,et al.Effect of IFN-gamma-endostatin gene therapy in combination with X-rays on inhibition of primary breast tumor growth and lung metastases in a murine model[J].Chinese Journal of Radiological Medicine and Protection,2010,30(4):387-390 |
| Effect of IFN-gamma-endostatin gene therapy in combination with X-rays on inhibition of primary breast tumor growth and lung metastases in a murine model |
| Received:May 26, 2010 |
| DOI：10.3760/cma.j.issn.0254-5098.2010.04.003 |
| KeyWords:Gene-radio therapy IFN-γ Endostatin |
| FundProject:国家自然科学基金(C03031804) |
| Author Name | Affiliation | E-mail | | LIU Lin-lin | Department of Biological Treatment, 2nd Hospital of Jilin University, Changchun 130021, China | linlinliucn@yahoo.com.cn | | CHANG Xiao-min | Department of Biological Treatment, 2nd Hospital of Jilin University, Changchun 130021, China | | | ZHANG Qi | Department of Biological Treatment, 2nd Hospital of Jilin University, Changchun 130021, China | | | ZHANG Wei-jing | Department of Biological Treatment, 2nd Hospital of Jilin University, Changchun 130021, China | | | LI Xiu-yi | 130021 长春, 吉林大学公共卫生学院 | | | WANG Tie-jun | 130021 长春, 吉林大学第二医院放疗科 | |
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| Abstract:: |
| Objective To evaluate the antitumor effects of interferon (IFN)γ-endostatin based gene radiotherapy in a metastatic breast tumor model of mice, and to elucidate the possible mechanisms involved.Methods Murine mammary adenocarcinoma 4T1 cells transfected with pEgr-IFN-γ and pEgr-endostatin plasmids were irradiated with 2-20 Gy of X-rays. IFN-γ and endostatin levels in the culture supernatants were measured. Female BALB/c mice were inoculated with 1×105 of 4T1 cells by mammary fat pad injection,and divided randomly into control, empty vector, gene therapy (pEgr-IFN-γ and pEgr-endostatin), radiotherapy, and combined gene-radiotherapy groups. Tumor/body weight ratio, lung metastases, and survival of the tumor-bearing mice were observed. Splenic cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell activity and intratumor microvessel density were also assessed. Results Irradiation significantly enhanced the section of IFN-γ and endostatin from the transfected 4T1 cells. Compared with gene therapy or radiotherapy alone,combined gene-radiotherapy resulted in the maximal attenuation in tumor growth rate,lung metastases and increased survival. The activities of CTL and NK cells were significantly enhanced and intratumor microvessel density reduced(t=2.120-22.140,P<0.05). Conclusions IFN-γ-endostatin-based gene-radiotherapy could provide a potential antitumor effect in a murine metastatic breast tumor model, which may be related to IFN-γ-stimulated CTL and NK cell activation, and endostatin-induced antiangiogenic activity. Gene-radiotherapy could serve as a neoadjuvant therapy for the locally advanced breast cancer. |
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