平阳霉素与抗Ⅳ型胶原酶单抗3G11联合使用的抗肿瘤作用  

Antitumor effect of pingyangmycin in combination with monoclonal antibody 3G11 directed against type Ⅳ collagenase

作　　者：刘秀均[1] 欧阳志钢[1] 戴垚[1] 刘小云[1] 甄永苏[1] 

机构地区：[1]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050

出　　处：《中华肿瘤防治杂志》2007年第3期177-180,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：高等学校全国优秀博士学位论文作者专项资金(200266)

摘　　要：目的:观察平阳霉素(PYM)与抗Ⅳ型胶原酶单抗3G11联合使用的抗肿瘤作用。方法:用ELISA法测定单抗3G11的免疫结合活性,MTT法测定PYM与3G11联合使用对肿瘤细胞的增殖抑制作用,用小鼠移植性肝癌22(H22)实验模型观察PYM与3G11联合使用的体内抗肿瘤作用。结果:单抗3G11具有结合靶抗原Ⅳ型胶原酶和小鼠肝癌22、人肝癌HepG2及人前列腺癌DU145细胞的能力,平阳霉素与3G11联合使用对上述细胞显示出比单独使用PYM具有更强的细胞增殖抑制作用。对小鼠移植性肝癌22,皮下接种肿瘤24 h后开始静脉注射给药治疗,隔天1次,共6次。实验第14天,PYM(10 mg/kg)与单抗3G11(60 mg/kg)联合使用的抑瘤率为85.4%。而PYM(10 mg/kg)抑瘤率为70.0%,单抗3G11(60 mg/kg)剂量的抑瘤率为49.6%。与单独使用同等剂量的PYM以及单抗3G11相比,PYM与单抗3G11联合使用显示出更强的肿瘤生长抑制作用。结论:PYM与3G11联合使用,对肿瘤细胞表现出的细胞增殖抑制作用以及对小鼠移植性肝癌22的抑瘤作用均强于单独的PYM与3G11,提示联合应用的前景。ABSTRACT OBJECTIVE, To study the antitumor effects of the combination of pingyangmycin （PYM） and monoclonal antibody（mAb） 3Gll directed against type Ⅳ collagenase. METHODS： Immunoreactivity of mAb 3Gll to type Ⅳ collagenase and various tumor cells was determined by ELISA and the cytotoxicity of PYM and PYM plus 3Gll was examined by MTT assay. Antitumor effects in vivo were evaluated by using subcutaneously transplanted hepatoma 22 tumor model in mice. RESULTS： mAb 3G11 showed immunoreactivity to type Ⅳ collagenase, mouse hepatoma 22 （H22） cells, human hepatoma HepG2 cells, and human prostatic carcinoma DU145 cells. As compared with free PYM, PYM plus 3G11 showed stronger cytotoxicity to these tumor cells. Synergetic effect was found at a certain dose range. When administered intravenously （iv× 6, every other day）, PYM （10 mg/kg） plus 3G11 （60 mg/kg） inhibited the subcutaneous growth of hepatoma 22 in mice by 85.4%, whereas free PYM at 10 mg/kg and mAb 3G11 at 60 mg/kg used separately inhibited tumor growth by 70.0% and 49.6%, respectively. CONCLUSIONS： PYM in combination with mAb 3G11 shows much stronger antitumor effects than equivalent doses of free PYM or mAb 3G11. The combination might be potentially useful in cancer therapy.

关 键 词：肝肿瘤/病理学 博莱霉素/药理学 抗体 单克隆 小鼠 裸 细胞系 肿瘤 

分 类 号：R73-3[医药卫生—肿瘤]