低剂量辐射联合阿霉素对荷乳腺癌裸鼠移植瘤生长及其移植瘤组织中HIF-1α和VEGF表达的影响

Effects of low-dose radiation combined with adriamycin on growth of transplantation tumor cells,HIF-1α and VEGF expressions in transplantation tumor tissue of breast cancer-bearing nude mice

目的:探讨低剂量辐射(LDR)联合阿霉素(ADM)对荷乳腺癌裸鼠移植瘤生长及移植瘤组织缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)表达的影响,阐明LDR联合ADM增强机体抗肿瘤作用的机制。方法:24只荷乳腺癌裸鼠随机分为假照组(0mGy)、LDR组(75mGy)、ADM组和LDR-6h-ADM组(LDR后6h给予ADM),各组荷瘤裸鼠以不同方式处理4d后全部处死,测量各组小鼠瘤质量,计算抑瘤率,光镜下观察肿瘤组织形态学表现,应用免疫组织化学方法检测肿瘤组织中HIF-1α和VEGF表达。结果:与假照组比较,其余各组小鼠平均瘤质量均明显降低(P<0.05),LDR-6h-ADM组小鼠平均瘤质量最低,但与LDR组和ADM组比较差异无统计学意义(P>0.05);LDR-6h-ADM组小鼠抑瘤率显著高于ADM组和LDR组(P<0.05)。组织形态学观察,各组小鼠肿瘤组织均见癌细胞分布,LDR-6h-ADM组可见癌细胞片状坏死,癌组织间质疏松,癌细胞坏死程度较ADM组和LDR组明显。免疫组织化学,假照组VEGF和HIF-1α蛋白表达水平最高,LDR-6hADM组最低。与假照组比较,其余各组小鼠肿瘤组织HIF-1α和VEGF平均灰度值明显升高,即蛋白表达水平明显降低(P<0.05)。结论:LDR联合ADM可使机体抗肿瘤作用增强,可能与LDR降低肿瘤组织HIF-1α和VEGF的表达、改善肿瘤缺氧及抑制肿瘤血管生成有关。

Objective To study the effects of low-dose radiation（LDR）combined with adriamycin（ADM）on the growth of transplantation tumor cells,hypoxia-inducible factor-1alpha（HIF-1α）and vascular endothelial growth factor（VEGF）expressions in transplantation tumor tissue of breast cancer-bearing nude mice,and to clarify the mechanism of enhancing anti-tumor effect of LDR combined with ADM.Methods Twenty-four breast cancerbearing nude mice were divided into sham irradiation group（0mGy）,LDR group（75mGy）,ADM group and LDR-6h-ADM group（administed with ADM 6hafter LDR）.The tumor weight was measured,the inhibitory rate of tumor was calculated,the morphology of tumor tissue was observed by light microscope,and the HIF-1αand VEGF expressions were detected with immunohistochemistry method.Results Compared with sham irradiation group,the mean tumor weights of the mice in other groups were decreased apparently（P〈0.05）.The mean tumor weight of the mice in LDR-6h-ADM group was the lowest,but had no significant differences when compared with LDR group and ADM group（P〉0.05）.The inhibitory rate of tumor of the mice in LDR-6h-ADM group was significantly higher than those in ADM group and LDR group（P〈0.05）.The pathological results showed that the cancer cells could be seen in each group,necrosis of cancer cells could be seen in LDR-6h-ADM group,the cancer tissue＇s interstitial was loose,and its extent of necrosis in cancer cells was significant compared with ADM and LDR groups.Compared with sham irradiation group,the mean gray values of HTF-1αand VEGF expressions in tumor tissue of mice were increased apparently in other groups（P〈0.05）.Conclusion LDR combined with ADM can enhance the body＇s anti-tumor effect,and the effect may be related to reducing the expressions of HIF-1αand VEGF,improving the hypoxia of tumor and inhibiting the formation of tumor angiogenesis.