西妥昔单抗增加结直肠癌细胞对125I粒子持续低剂量率照射的敏感性

目的 探讨在¹²⁵I 放射性粒子持续低剂量率照射下，西妥昔单抗对结直肠癌细胞CL187放射敏感性的影响及可能的机制。方法 实验将直肠癌细胞CL187分为空白对照组、单纯100 nmol/L C225处理组、单纯¹²⁵I -CLDR照射组和C225联合¹²⁵I -CLDR组。克隆形成实验检测C225是否影响人结直肠癌CL187细胞对¹²⁵I 放射性粒子持续低剂量率照射的放射敏感性。流式细胞仪检测C225对¹²⁵I -CLDR照射诱导的细胞凋亡的影响。细胞周期检测C225对细胞周期的调节。瑞氏姬姆萨染色检测有丝分裂指数。Western blot检测细胞内Bax、Bcl-2的水平。结果 100 nmol/L C225的放射增敏比为1.4，并能够增加¹²⁵I -CLDR照射诱导的细胞凋亡（t=6.6，P<0.05），增加Bax/Bcl-2比值。与空白对照组相比，单独C225处理可使CL187细胞G₁期阻滞（t=3.0，P<0.05），单纯¹²⁵I -CLDR照射组细胞也存在G₁期阻滞（t=8.5，P<0.01），两者联合时的G₁期阻滞效应与¹²⁵I -CLDR单独处理时相比，差异无统计学意义（t=0.8，P>0.05）。有丝分裂指数检测结果显示，各实验组与对照组相比差异无统计学意义。结论 C225可增加结直肠癌细胞CL187对¹²⁵I -CLDR照射的放射敏感性，机制可能是C225增加细胞内Bax/Bcl-2比值，增加¹²⁵I-CLDR诱导的细胞凋亡，与细胞周期阻滞和细胞周期检查点功能无关。

Enhancement of cetuximab on radiosensitivity of colorectal cancer cells exposed to 125I seeds

Objective To investigate the effect of cetuximab (C225) on the radiosensitivity of colorectal cancer cells CL187 and underlying mechanism. Methods Cell survival was detected by colony forming assay. The levels of apoptosis and cell cycle distribution were determined by flow cytometer. The mitotic ratio was measured by Wright's-Giemsa mixed coloring method. The protein levels of Bax and Bcl-2 were detected by Western blot. Results The sensitizing enhancement ratio of C225 was approximately 1.4. C225 treatment and ¹²⁵I seed radiation induced G₁ cell cycle arrest individually. C225 increased the radiation-induced apoptosis (t=6.6,P<0.05) and cellular Bax/Bcl-2 ratio (t=9.4, P<0.05), but did not increase radiation-induced G₁ arrest. In addition, there was no difference in mitotic index among different groups. Conclusions C225 sensitizes CL187 to ¹²⁵I seed irradiation, which might be related with increase of radiation-induced apoptosis.