持续小剂量化疗对A549肺癌PTEN基因和凋亡的影响  

Low-dose metronomic chemotherapy upregulates PTEN and induces apoptosis of A549 pulmonary adenocarcinoma in athymic mice

作　　者：李长毅[1] 张明川[1] 梅同华[1] 厉明[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010

出　　处：《第三军医大学学报》2007年第18期1760-1763,共4页Journal of Third Military Medical University

基　　金：重庆市卫生局资助课题(200453)~~

摘　　要：目的检测不同剂量环磷酰胺化疗后,荷A549肺腺癌裸鼠皮下肿瘤组织中PTEN的表达及癌细胞凋亡情况。方法右季肋部皮下注射A549细胞悬液,建立荷A549肺腺癌裸鼠模型,分3组,分别给予持续小剂量(low-dosemet-ronomic,LDM)、最大耐受剂量(maximum tolerable dose,MTD)CTX(环磷酰胺)和生理盐水化疗,21d治疗结束取皮下肿瘤组织,以免疫组化S-P法分别检测3组裸鼠皮下肿瘤组织中PTEN的表达,以TUNEL法检测癌细胞的凋亡。结果化疗14d后,LDM组瘤体生长明显慢于MTD组和对照组(P<0.05);化疗第7天开始,LDM组和MTD组裸鼠体质量开始出现减轻(P<0.05),第21天,MTD组裸鼠体质量显著减轻,3组裸鼠体质量两两相比均有统计学意义(P<0.05);LDM组PTEN阳性表达及凋亡率均显著高于大剂量组和对照组(P<0.05)。结论持续小剂量化疗可使癌组织中PTEN表达上调,从而诱导细胞凋亡增多。Objective To investigate the expression of PTEN protein and apoptosis of tumor cells in tumor graft of human pulmonary adenocarcinoma in athymic mice after chemotherapy （CTX）. Methods Eighteen athymic BALB/C-nu/nu mice were subcutanously injected under the anterior right leg with cultured A549 cell suspension. Then, all the athymic mice were randomized into 3 groups, respectively receiving 100 mg/kg CTX （ low-dose metronomic, LDM） each other day for 3 times, 20 mg · kg^ - 1· d ^- 1 CTX （ maximum tolerable dose, MTD） for 21 d and 0.9% NS for 21 d. All athymic mice were killed after chemotherapy, and the obtained tumors were used to detect the expression of PTEN protein by immunohistochemistry and the apoptosis of the tumor cells by TUNEL. Results The expression of PTEN protein and apoptosis rate in LDM group were significantly higher than that in MTD group and control group （P 〈 0.05 ）. Conclusion The low-dose metronomic chemotherapy can upgrade the level of PTEN protein so as to induce the apoptosis of tumor ceils consequently.

关 键 词：化疗 小剂量 肺癌 PTEN 凋亡 

分 类 号：R73-361[医药卫生—肿瘤] R730.22[医药卫生—临床医学]