摘要
背景与目的:姜黄素(curcumin)能有效增强放射线对肿瘤的作用,但其作用机制尚不清楚。该研究旨在探讨姜黄素是否对人乳腺癌MDA-MB-231细胞裸鼠移植瘤有放射增敏效应,并探讨其协同抑制效应的机制。方法:人乳腺癌裸鼠移植瘤模型建立成功后,将裸鼠随机分为4组:对照组、药物组、放射组和联合组(姜黄素+放射),每组6只;检测裸鼠移植瘤的体积及体质量,计算抑瘤率,并绘制移植瘤的生长曲线;免疫组织化学法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)表达;蛋白质印迹法(Western blot)检测基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)及缺氧诱导因子-1α(hypoxiainducible factor-1α,HIF-1α)的蛋白表达。结果:联合组的抑瘤率[(71.62±6.11)%]显著高于放射组[(41.76±5.84)%](P<0.05)。免疫组化结果显示,单纯放射不能使VEGF表达下调(P>0.05),姜黄素联合放射能明显抑制VEGF的表达(P<0.01)。Western blot结果显示,姜黄素与放射均可抑制MMP-9的表达,两者联用较单纯放射效果更加显著(P<0.05);单纯放射不能抑制HIF-1α的表达(P>0.05),姜黄素联合放射HIF-1α蛋白表达显著降低(P<0.01)。结论:姜黄素可以增强乳腺癌裸鼠移植瘤的放射敏感性,其机制可能是通过下调VEGF、MMP-9和HIF-1α的蛋白表达而发挥作用。
Background and purpose： Curcumin can enhance the radiation sensitivity on tumor effectively, but the mechanism of radiosensitization is still unclear. The present study aimed to investigate whether curcumin could enhance the radiation sensitivity on xenograft tumor of breast cancer of MDA-MB-231 cells in nude mice, and to investigate the underlying mechanism. Methods： Human breast cancer xenograft model on nude mice was established successfully, and the mice were divided into 4 groups： control group, curcumin group, radiation group, combination group （radiation＋curcumin） （6 mice each group）. The size and weight of xenograft tumor were detected, the tumor inhibition rate was calculated and the xenograft ~mor growth curve was depicted. Immunohistochemistry was adopted to detect the expression of VEGF. Western blot was used to detect the expression of MMP-9 and HIF-lcc Results： The tumor inhibition rate in the combination group [（71.62±6.11）%] was significantly higher than that in the radiation group [（41.76±5.84）%]（P〈0.05）. The result by immunohistochemistry showed that radiation therapy could not inhibit the expression of VEGF （P=0.05）, while curcumin and radiation combination inhibited the expression of VEGF （P〈0.01）. The result of Western blot showed that curcumin or radiation inhibited the expression of MMP-9, curcumin and radiation combination inhibited the expression of MMP-9 more significantly （P〈0.05）. Radiation could not inhibit the expression of HIF-1 α （P〉0.05）, curcumin and radiation combination inhibited the expression of VEGF significantly （P〈0.01）. Conclusion： Curcumin can enhance the radiosensitivity in nude mice xenografts of breast cancer, and the mechanism involves the down-regulation of VEGF, MMP-9 and HIF-1α.
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2012年第5期342-346,共5页
China Oncology
基金
湖南省中医药科研计划项目(NO:2010087)
