Anti-tumor effect of IFNγ endostatin gene-radiotherapy in vivo and its mechanism

Objective: To study the anti-tumor effect of pEgr-IFN γ-endostatin gene-radiotherapy in mice bearing Lewis lung carcinoma and its mechanism. Methods: The plasmids packed by liposome were injected locally into the tumors of the mice, and the tumors were irradiated with 5 Gy X-rays 36 hours later. The tumor growth rate at different times and the mean survival period of the mice were observed. Cytotoxic activity of splenic CTL, NK and TNFα secretion activity of peritoneal macrophages of the mice in various groups were evaluated 15 days after irradiation. The intratumor microvessel density was evaluated by immunohistochemical staining 10 days after irradiation. Results: The tumor growth rate of the mice in double-gene-radiotherapy group was significantly lower than that of the control group, 5 Gy X-irradiation alone group and single-gene-radiotherapy group 6-18 days after gene-radiotherapy, and the mean survival period of which was longer. The tumor growth rate in mice treated with pEgr-IFN γ-endostatin and 2.5 Gy X-ray irradiation for four times was lower significantly than that in mice treated with pEgr-IFN γ-endostatin and 10 Gy X-irradiation for once only 12-18 days after therapy, and the mean survival time of mice was longer. Cytotoxic activity of splenic CTL, NK and TNF α secretion activity of peritoneal macrophages of the mice in the double-gene-radiotherapy group were significantly higher than those in the control group, 5 Gy X-irradiation alone group and pEgr-endostatin gene-radiotherapy group 15 days after irradiation. The intratumor microvessel density of the mice in double-gene-radiotherapy group was significantly lower than that in the control group, 5 Gy X-irradiation alone group and pEgr-IFNγ gene-radiotherapy group. Conclusions: The anti-tumor effect of double-gene-radiotherapy is significantly better than that of single-gene-radiotherapy. Its mechanism is perhaps associated with the expressions of IFNγ and endostatin induced by X-ray irradiation, which enhence anti-tumor immunologic function and anti-angiogenesis function. The anti-tumor effect of repeated low dose double-gene-radiotherapy is better than that of high dose double-gene-radiotherapy for once only. (authors)