杨巍,朴春姬,刘林林,田梅,吕喆,李修义.γ干扰素和内皮抑素双基因-放射治疗的体内抑瘤效应及其机制[J].中华放射医学与防护杂志,2005,25(4):325-328 |
γ干扰素和内皮抑素双基因-放射治疗的体内抑瘤效应及其机制 |
Anti-tumor effect of IFNγ endostatin gene-radiotherapy in vivo and its mechanism |
投稿时间:2005-01-28 |
DOI: |
中文关键词: γ干扰素 内皮抑素 基因-放射治疗 Lewis肺癌细胞 X射线 |
英文关键词:IFNγ Endostatin Gene-radiotherapy Lewis lung carcinoma X-ray |
基金项目:国家自然科学基金资助项目(30170290) |
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中文摘要: |
目的 探讨γ干扰素和内皮抑素双基因放射治疗在荷Lewis肺癌小鼠的体内抑瘤效应及其机制。方法 小鼠肿瘤局部注射脂质体包裹的质粒后36h,接受5GyX射线照射,观察各组小鼠照射后不同时间肿瘤生长速率和平均存活时间;照射后第15天检测各组小鼠脾脏CTL、NK细胞毒活性和腹腔巨噬细胞TNFα分泌活性,照射后第10天用免疫组化法检测肿瘤组织微血管密度。结果 基因放射治疗后第6~18天,双基因放射治疗组小鼠肿瘤生长速率明显低于对照组、单纯放疗组及单基因放射治疗组,且平均生存时间明显延长。治疗后第12~18天,4次(双基因质粒+2.5Gy)组肿瘤生长速率明显低于双基因质粒+10Gy组,且平均生存时间明显延长。照射后第15天双基因放射治疗组小鼠脾脏CTL、NK细胞毒活性和腹腔巨噬细胞TNFα分泌活性均明显高于对照组、单纯放疗组及内皮抑素单基因放射治疗组,肿瘤组织微血管密度明显低于对照组、单纯放疗组及γ干扰素单基因放射治疗组。结论 双基因放射治疗抑瘤效应明显优于单基因放射治疗,其机理可能与辐射诱导γ干扰素和内皮抑素表达,提高机体抗肿瘤免疫功能和抗肿瘤血管生成作用有关。多次小剂量双基因放射治疗的抑瘤效应优于单次大剂量双基因放射治疗。 |
英文摘要: |
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-IFN γ 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 IFN γ 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. |
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