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在肺癌临床前模型中,大豆异黄酮增强高强度放疗和保护肺组织的差异效应。

Differential effect of soy isoflavones in enhancing high intensity radiotherapy and protecting lung tissue in a pre-clinical model of lung carcinoma.

机构信息

Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, USA.

出版信息

Radiother Oncol. 2013 Oct;109(1):117-25. doi: 10.1016/j.radonc.2013.08.015. Epub 2013 Sep 7.

Abstract

BACKGROUND

Radiotherapy of locally-advanced non-small cell lung cancer is limited by radiation-induced pneumonitis and fibrosis. We have further investigated the role of soy isoflavones to improve the effect of a high intensity radiation and reduce lung damage in a pre-clinical lung tumor model.

METHODS

Human A549 NSCLC cells were injected i.v. in nude mice to generate a large tumor burden in the lungs. Mice were treated with lung irradiation at 10 Gy and with oral soy. The therapy effect on the tumor cells and surrounding lung tissue was analyzed on lung sections stained with H&E, Ki-67 and Masson's Trichrome. Pneumonitis and vascular damage were evaluated by measurements of alveolar septa and immunofluorescent staining of vessel walls.

RESULTS

Combined soy and radiation caused a significantly stronger inhibition of tumor progression compared to each modality alone in contrast to large invasive tumor nodules seen in control mice. At the same time, soy reduced radiation injury in lung tissue by decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and vessels.

CONCLUSIONS

These studies demonstrate a differential effect of soy isoflavones on augmenting tumor destruction induced by radiation while radioprotecting the normal lung tissue and support using soy to alleviate radiotoxicity in lung cancer.

摘要

背景

局部晚期非小细胞肺癌的放射治疗受到放射性肺炎和纤维化的限制。我们进一步研究了大豆异黄酮的作用,以提高高强度辐射的效果并减少临床前肺肿瘤模型中的肺损伤。

方法

将人 A549 NSCLC 细胞静脉注射到裸鼠中,在肺部产生大的肿瘤负担。用 10 Gy 的肺部照射和口服大豆治疗小鼠。用 H&E、Ki-67 和 Masson 三色染色的肺切片分析对肿瘤细胞和周围肺组织的治疗效果。通过测量肺泡间隔和血管壁的免疫荧光染色评估肺炎和血管损伤。

结果

与对照组小鼠中所见的大侵袭性肿瘤结节相比,大豆与放射联合治疗显著增强了对肿瘤进展的抑制作用,而放射单独治疗则没有。同时,大豆通过减少肺炎、纤维化和保护肺泡间隔、细支气管和血管来减轻肺组织的放射损伤。

结论

这些研究表明,大豆异黄酮对增强辐射诱导的肿瘤破坏具有不同的作用,同时保护正常肺组织,并支持使用大豆来减轻肺癌的放射毒性。

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