| 刘林林,常晓敏,张奇,张伟静,李修义,王铁君.IFN-γ和内皮抑素双基因联合X射线对小鼠乳腺癌及肺转移的抑瘤作用[J].中华放射医学与防护杂志,2010,30(4):387-390 |
| IFN-γ和内皮抑素双基因联合X射线对小鼠乳腺癌及肺转移的抑瘤作用 |
| 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 |
| 投稿时间：2010-05-26 |
| DOI：10.3760/cma.j.issn.0254-5098.2010.04.003 |
| 中文关键词: 基因-放射治疗 内皮抑素 干扰素-γ |
| 英文关键词:Gene-radio therapy IFN-γ Endostatin |
| 基金项目:国家自然科学基金(C03031804) |
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| 中文摘要: |
| 目的 评价IFN-γ和内皮抑素(endostatin)双基因-放射治疗在小鼠转移性乳腺癌中的抑瘤效应,并探讨其可能的作用机制。方法 用脂质体包裹pEgr-IFN-γ和 pEgr-endostatin质粒转染小鼠乳腺腺癌4T1 细胞,并用X射线照射,吸收剂量为2~20 Gy。用ELISA检测细胞培养液上清中IFN-γ和内皮抑素的浓度。小鼠下肢注4T1肿瘤细胞1×105个,荷瘤小鼠随机分组为对照组、空质粒组,基因治疗组、放射治疗组及基因-放射治疗组,观察小鼠肿瘤生长及肺转移情况,计算肿瘤生长率、肿瘤/体重比及荷瘤小鼠生存率, 并用流式细胞仪检测脾脏 CTL 和 NK细胞的细胞毒活性,用免疫组织化学法检测肿瘤内部的微血管密度。结果 辐射显著增强了4T1 细胞分泌IFN-γ和内皮抑素的浓度。小鼠接受基因-放射治疗与单独接受基因治疗或者接受放射治疗相比,肿瘤生长率明显降低,同时生存率明显提高(t＝8.724,P<0.05)。双基因联合放射治疗组小鼠脾中CTL 和 NK 细胞的细胞毒活性及腹腔巨噬细胞的TNF-α水平较对照组明显升高(t=2.120、22.140和5.289,P<0.05),微血管密度明显降低(t=13.294,P<0.05)。结论 IFN-γ和内皮抑素的基因-放射治疗增强了小鼠转移性乳腺癌的抑瘤效应,其机制可能与IFN-γ激活 CTL 和 NK 细胞活性及内皮抑素引起肿瘤血管生成抑制有关。 |
| 英文摘要: |
| 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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