放射联合常山酮增强肺癌疗效及机制动物实验研究

Role of radiotherapy combined with halofuginone in enhancing therapeutic effect on Lewis lung cancer transplanted in mice and related mechanisms

目的探讨放射联合常山酮对增强Lewis肺癌小鼠移植瘤疗效及对肿瘤侵袭转移的影响，并探索可能的分子机制。方法将Lewis肺癌移植瘤小鼠随机分为空白对照组、常山酮组、放射组及联合组（9只／组），处理结束后第3天，每组随机处死4只小鼠行免疫组化及ELISA检查，剩余小鼠继续观察存活时间及肝、肺转移情况。组间差异采用方差分析。结果处理第9天，对照组、常山酮组、放射组及联合组小鼠平均肿瘤体积分别为175．2、118．5、106．6、85．6mm。（P=0．000）。4个组中位存活时间分别为39、61．5、78．5、84．5d（P=0．002）。联合组肝肺转移数目显著最少。免疫组化及ELISA结果显示TGF-β1，水平放射组较对照组升高，联合组较对照组低；肿瘤平均血管密度计数联合组明显少于放射组。对照组及放射组胶原蛋白表达较高，常山酮组及联合组胶原蛋白表达较低。结论放射联合常山酮可能会增强肿瘤治疗疗效，其潜在的机制需要进一步研究。

Objective To investigate the role of radiotherapy combined with halofuginone in enhancing the therapeutic effect on Lewis lung cancer （LLC） and influence on tumor invasion and metastasis, and to explore possible molecular mechanisms. Methods The model mice with LLC xenograft were randomly divided into blank control group, halofuginone group, irradiation group, and combination group. On day 3 after the treatment ended, 4 mice in each group were randomly sacrificed, and immunohistochemistry and enzyme-linked immunosorbent assay （ELISA） were performed. The other mice were observed for survival time and liver/lung metastases. Analysis of variance was applied for comparison of results between groups. Results On the ninth day of treatment, the mean tumor volume was 175.2 mm3 in the blank control group, 118. 5 mm3 in the halofuginone gronp, 106. 6 mm3 in the irradiation group, and 85.6 mm3 in the combination group （P = 0. 000）. The median survival times for these groups were 39 days, 61.5 days, 78. 5 days, and 84. 5 days, respectively （P= 0. 002）. The combination group had the lowest number of liver and lung metastases. The results of immunohistochemistry and ELISA showed that compared with the blank control group, the irradiation group had a higher level of transforming growth factor-β1 （TGF- β1 ）, while the combination group had a lower level of TGF-β1. The combination group had a lower mean tumor vascular density than the blank control group. The blank control group and the irradiation group had higher expression levels of collagen, while the halofuginone group and the combination group had lower expression levels of collagen. Conclusions Radiotherapy combined with halofuginone may enhance the effect of antitumor therapies, and potential mechanisms still need further investigation.