β-榄香烯对人肺腺癌裸鼠移植瘤放疗增敏作用与HIF-1α CAⅨ的相关性研究  

Radiosensitization by P-elemene of Transplanted Lung Adenocarcinoma Cells in Nude Mice is Related to the Expression of HIF-la and CAK

作　　者：李国权[1] 谢冰冰[1] 陈英海[1] 李小龙[2] 邹丽娟[1] 

机构地区：[1]大连医科大学附属二院肿瘤放疗科,辽宁省大连市116027 [2]西安市解放军第323医院肿瘤放疗中心

出　　处：《中国肿瘤临床》2011年第6期312-315,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30770646);辽宁省教育厅创新团队项目计划资助(编号:2008T031)

摘　　要：目的:建立人肺腺癌A549细胞株裸鼠移植瘤模型,研究β-榄香烯对移植瘤的放疗增敏效应,寻找最佳增敏剂量,并探讨放疗增敏机制是否与HIF-1α、CAⅨ具有相关性。方法:采用细胞悬液接种法建立裸鼠移植瘤模型,待移植瘤体积达0.8～1.0 cm^3时,将裸鼠随机分组,观测各组移植瘤的体积倍增时间。通过计算增敏系数,获得最佳增敏剂量。RT-PCR及免疫组化方法检测HIF-1α表达,免疫组化检测CAⅨ的表达。结果:成功建立裸鼠移植瘤模型。25、45、100mg/kg三种浓度β-榄香烯的增敏系数EF值分别为0.84、1.24、2.04,最佳增敏剂量为45 mg/kg。药物组、放疗组与空白组比较,HIF-1 αmRNA表达明显增强(P<0.01),药物组与放疗组之间HIF-lαmRNA表达没有差异(P>0.05),联合组与其他各组比较,HIF-1αmRNA表达明显降低(P<0.01)。各组HIF-1α的免疫组化情况:药物组与空白组比较HIF-1α表达略增强(P>0.05);放疗组与空白组比较HIF-1α表达明显增强(P<0.05),联合组与其他各组比较HIF-1α表达明显降低(P<0.01)。各组CAⅨ的免疫组化情况:放疗组与空白组比较CAⅨ表达略增强(P>0.05),药物组与空白组比较CAⅨ表达增强(P<0.05),联合组与其他各组比较,CAⅨ表达明显降低(P<0.05)。结论:本研究证实β-榄香烯的最佳增敏剂量为45 mg/kg,与放疗联合明显抑制HIF-1α、CAⅨ的表达,提示β-榄香烯通过改善乏氧状况达到放射增敏的作用,值得进一步研究。Objective： To establish a nude mouse model transplanted with the A549 lung adenocarcinoma cell line, to study the change in radiosensitivity of transplanted tumors treated by β-elemene, to obtain the optimal dose to enhance the radiosensitivity of transplanted amaors, and to investigate the association between radiosensitization by β-elemene and the expression of HIF- 1 a and CA IX. Methods： The nude mouse model transplanted with A549 lung adenocarcinoma cells was established by inoculating with a cell suspension. When the transplanted tumor size reached 0.8-1.0 cm^3, the nude mice were randomly grouped （ 5 per group ） and the volume doubling time was observed. The EF values were calculated and the optimal dose to enhance the radiosensitivity of transplanted tumors was obtained. The expression of HIF-1 α was assessed by RT-PCR and immunohistochemistry. The expression of CA IX was detected by immunohistochemistry. Results： A nude mouse model transplanted with the A549 lung adenocarcinoma cell line was successfully established. The EF were 0.84 （ 25 mg/kg β-elemene ）, 1.24 （ 45 mg/kg β-elemene ） and 2.04 （ 100 mg/kg β-elemene ） and the optimal dose to enhance radiosensitivity of the transplanted tumor was 45 mg/kg. According to RT-PCR the expression of HIF-1 a was significantly increased in the groups treated with β-elemene or radiation alone compared with the control group （ P 〈 0.01 ）, and there was no difference between the β-elemene and radiation groups （ P 〉 0.05 ）. According to RT-PCR the expression of HIF-1 u was greatly decreased in the co-treatment group compared with the control group （ P 〈 0.01 ）. The results of immunohistochemistry of HIF-1 α showed no difference between the group treated with β-elemene alone and the control group （ P 〉 0.05 ）, the expression of HIF-1 ct in the group treated with radiation alone was higher than that in the control group （ P 〈 0.05 ）, and the co-treatment group had the lowest expression of all groups （ P 〈

关 键 词：Β-榄香烯 移植瘤 放疗增敏 HIF-1Α CAⅨ 

分 类 号：R734.2[医药卫生—肿瘤]