^(125)I粒子组织间植入对大肠癌的抑制作用及其机制

Iodine-125 interstitial brachytherapy in colorectal cancer inducing apoptosis

目的探讨125I粒子抑制大肠癌生长的作用及其机制。方法采用雄性BALB/C裸小鼠建立人类大肠癌HCT-8细胞株的裸小鼠皮下移植瘤模型,将荷瘤鼠分5组(每组10只),对照组、空剂量组(0Bq)、低剂量组(7.4×106Bq)、中剂量组(14.8×106Bq)、高剂量组(29.6×106Bq),原位末端标记法检测肿瘤细胞凋亡的情况,免疫组织化学SP法染色检测血管内皮生长因子(VEGF),行微血管密度记数(MVD),同时检测p53蛋白表达情况。结果125I粒子组织间植入治疗大肠癌,高、中、低剂量组抑瘤率分别为46.2%、34.0%、21.5%。在高剂量组中,p53蛋白表达增加,凋亡细胞增多,MVD及VEGF减少。结论(1)确证了125I粒子对大肠癌治疗的有效性。(2)125I粒子的推荐剂量14.8×106~29.6×106Bq。(3)125I粒子组织间植入抑制肿瘤新生血管生成,同时p53蛋白表达量增加,细胞凋亡增多。

Objectives To study the inhibition of iodine-125 on the growth of colorectal cancer cells and the mechanism, Methods The animal models of the HCT-8 tumor were estabilished first through the injection of the ceils into nude mice sbcutaneously, followed by the implant of the iodine-125 granules at different dosages into the tumor mass, The animals were divided into 5 groups （10 nude mice in each group）, receiving different dosages of iodine-125 granules respectively （high-, middle-, low-, zero-, control）. TUNEL method was used to detect the apoptosis of tumor cells. Immunohistochemistry S-P staining was used to measure the VEGF and p53 protein. Microvascular density was recorded. Results In the in vivo study, the inhibitary rate in high, middle and low dosage groups in the HCT-8 nude mouse tumor model was 46.2 %, 34.0% and 21.5 % respectively. The expression of p53 protein and apoptosis were increased, while MVD and VEGF was reduced in high dosage group. Conclusion （ 1 ） This study verifies the efficiency of the iodine-125 granules in inhibiting the growth of colorectal cancer; （2） The dosage range of iodine-125 is between 0.4 and 0.8 mCi; （3） Iodine-125 interstitial hrachytherapy inhihites vascularization and induces the expression of p53.