沙利度胺联合放射治疗对结肠癌小鼠移植瘤生长及放射敏感性的影响

背景与目的：沙利度胺能有效增强肿瘤对放射的敏感性，但作用机制尚不清楚。本研究探讨沙利度胺对人结肠癌小鼠移植瘤放射敏感性的影响，并探讨其协同抑制效应的机制。方法：建立colon26结肠癌移植瘤模型，将32只小鼠随机分为对照组；单纯沙利度胺组(T组)；单纯放疗组(R组)；沙利度胺+放疗组(T+R组)；从治疗当天开始，隔日测量肿瘤体积，绘制肿瘤生长曲线,治疗结束时测量肿瘤体积，计算抑瘤率，处死小鼠后剥离瘤体，采用免疫组化法测定各组肿瘤组织微血管密度(microvesseldensity，MVD)。结果：治疗第22天，对照组、T组、R组和T+R组移植瘤平均体积分别为(4.97±1.20)cm3、(2.90±0.92)cm3、(2.66±0.88)cm3和(1.89±0.76)cm3；肿瘤生长抑制率分别为41.7%、46.5%和61.9%，T+R组移植肿瘤抑瘤率明显高于其他各组(P＜0.05)；与R组比较，T+R组的放射增敏率为2.27；沙利度胺联合放射治疗能显著抑制肿瘤组织MVD生成：T+R组的平均MVD较对照组下降了46.8%，下降程度明显高于T组(40.7%)和R组(37.7%，P＜0.05)；且T+R组肿瘤组织中出现较多的坏死，坏死细胞数明显高于对照组(P＜0.05)。结论：沙利度胺可以增强结肠癌小鼠移植瘤的放射敏感性，其机制可能与抑制移植瘤血管的生成有关。

The effect of thalidomide combined with radiation therapy on growth and radiosensization on xenograft tumor of colonic carcinoma

Background and purpose: Thalidomide can enhance the radiation sensitivity on tumor effectively, but the mechanism of radiosensitization is still unclear. The present study aimed to investigate whether thalidomide could enhance the radiation sensitivity on colon cancer transplanted tumor of mouse, and to investigate the underlying mechanism. Methods: We established the model of colon26 colonic carcinoma, and the mice were divided into 4 groups: Control group, the thalidomide group, the radiotherapy group and thalidomide+radiotherapy group. From the day of treatment, tumors were measured every other day. Then, the xenograft tumor growth curve was depicted. Tumor volumes were measured in different treatment groups, then, the inhibitory rates of tumor growth were calcutated. Using immunohistochemical method in to detect the expression of microvessel density (MVD) in tumor tissue. Results: The mean tumor volumes at day 22 were (4.97±1.20)cm3 (control group), (2.90±0.92)cm3 (T group), (2.66±0.88)cm3 (R group), and (1.89±0.76)cm3 (T+R group). The tumor inhibition rate in the combination group (61.9%) was significantly higher than the other groups (41.7%, 46.5%, P<0.05). The radiotherapy sensitization enhancement ratio of the combined treatment group was 2.27 times than in the radiotherapy group. Thalidomide combined with radiation therapy can significantly inhibit microvessel density of tumor: The decreasing MVD of T+R group, T group and R group were respectively 46.8%, 40.7% and 37.7%, and there was statistical significance between T+R group and T group (P<0.05 ), so as between T+R group and R group. It could be found more necrotic cells in tumor of group, and there was statistical significance between T+R group and control group (P<0.05). Conclusion: Thalidomide can enhance the radiosensitivity mice of colonic carcinoma, and its mechanism may be related to the inhibition of tumor angiogenesis related.