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首页> 外文期刊>Annals of surgical oncology >Combined IFN-gamma-endostatin gene therapy and radiotherapy attenuates primary breast tumor growth and lung metastases via enhanced CTL and NK cell activation and attenuated tumor angiogenesis in a murine model.
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Combined IFN-gamma-endostatin gene therapy and radiotherapy attenuates primary breast tumor growth and lung metastases via enhanced CTL and NK cell activation and attenuated tumor angiogenesis in a murine model.

机译：IFN-γ-内皮抑素基因治疗与放射治疗相结合，可通过增强CTL和NK细胞的激活并减轻鼠模型中的肿瘤血管生成来减轻原发性乳腺肿瘤的生长和肺转移。

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BACKGROUND: Gene-radiotherapy, a combination of gene therapy and radiotherapy, is a new paradigm for cancer treatment, with the potential to simultaneously improve local and systemic breast cancer control. The aim of this study was to evaluate antitumor effect of interferon (IFN)-gamma-endostatin-based gene-radiotherapy in a murine metastatic breast tumor model, and to elucidate possible mechanisms involved. METHODS: Murine mammary adenocarcinoma 4T1 cells transfected with pEgr-IFN-gamma and pEgr-endostatin plasmids were irradiated (2-20 Gy). IFN-gamma and endostatin levels in the culture supernatants were measured. In vivo female BALB/c mice were inoculated with 1 x 10(5) 4T1 cells by mammary fat pad injection and divided into control, empty vector, gene therapy (pEgr-IFN-gamma and pEgr-endostatin), radiotherapy, and combined gene-radiotherapy groups. Tumor growth, 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 IFN-gamma and endostatin secretion from the transfected 4T1 cells. In vivo mice that received combined gene-radiotherapy showed maximal attenuation in tumor growth rate and lung metastases with increased survival compared with mice that received gene therapy or radiotherapy alone. This was associated with significantly enhanced CTL and NK cell activity and reduced intratumor microvessel density. CONCLUSION: These results demonstrate that IFN-gamma-endostatin-based gene-radiotherapy provide a potent antitumor effect in a murine metastatic breast tumor model, which may relate to IFN-gamma-stimulated CTL and NK cell activation, and endostatin-induced antiangiogenic activity. Thus, gene-radiotherapy may represent a useful addition to neoadjuvant management of locally advanced breast cancer.
机译：背景：基因放射疗法是基因疗法和放射疗法的结合，是一种新的癌症治疗范例，具有同时改善局部和全身性乳腺癌控制的潜力。这项研究的目的是评估在小鼠转移性乳腺肿瘤模型中基于干扰素（IFN）-γ-内皮抑素的基因放射疗法的抗肿瘤作用，并阐明可能的机制。方法：用pEgr-IFN-γ和pEgr-内皮抑素质粒转染小鼠乳腺腺癌4T1细胞（2-20 Gy）。测量培养上清液中的IFN-γ和内皮抑素水平。体内雌性BALB / c小鼠通过乳腺脂肪垫注射接种1 x 10（5）4T1细胞，分为对照组，空载体，基因治疗（pEgr-IFN-γ和pEgr-endostatin），放疗和联合基因-放疗组。观察肿瘤生长，肿瘤/体重比，肺转移和荷瘤小鼠的存活。还评估了脾细胞毒性T淋巴细胞（CTL）和自然杀伤（NK）细胞活性以及肿瘤内微血管密度。结果：辐射显着增强了转染的4T1细胞的IFN-γ和内皮抑素分泌。与单独接受基因治疗或放疗的小鼠相比，接受基因放射治疗的体内小鼠显示出最大的肿瘤生长速率和肺转移衰减，并具有增加的生存期。这与显着增强的CTL和NK细胞活性以及降低的肿瘤内微血管密度有关。结论：这些结果表明，基于IFN-γ-内皮抑素的基因放射疗法在小鼠转移性乳腺肿瘤模型中提供了有效的抗肿瘤作用，这可能与IFN-γ刺激的CTL和NK细胞活化以及内皮抑素诱导的抗血管生成活性有关。 。因此，基因放射疗法可能是局部晚期乳腺癌新辅助治疗的有用补充。

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