摘要
目的观察131I标记血管内皮生长因子受体-3(vascular endothelial growth factor receptor-3,VEGFR-3)高亲和融合多肽(phage-SHSWHWLPNLRHYAS)对荷人卵巢癌小鼠移植瘤的靶向治疗作用。方法用Iodogen法合成131I-多肽及131I-单抗,体外分别与人淋巴管内皮细胞(LEC)共培养,MTT法检测其对LEC细胞生长的抑制作用;体内44只裸鼠经皮下接种卵巢癌细胞株,成瘤后2周,将20只荷瘤小鼠按随机数字表法分成4组,每组5只。分别经尾静脉注射,Ⅰ组:多肽4.4μg/只,Ⅱ组:131I-多肽7.4MBq/只,Ⅲ组:131I-单抗7.4MBq/只,Ⅳ组:生理盐水0.2ml作为对照组。干预后每周测量1次小鼠肿瘤的长径及短径,观察4周。余24只荷瘤鼠瘤体达1cm后行SPECT显像。结果体外131I多肽组对LEC细胞的生长抑制率在72h达到最高,131I单抗组对LEC细胞的生长抑制率在96h达到最高;72h及96h131I多肽组与131I单抗组及多肽组比较抑制率差异均有统计学意义(P<0.05);体内4周治疗结束时,Ⅰ、Ⅱ、Ⅲ、Ⅳ组小鼠肿瘤的体积分别为(723±164)、(291±68)、(457±88)、(792±112)mm3,其中Ⅱ、Ⅲ组与Ⅳ组肿瘤体积相比差异有统计学意义(P<0.05),而Ⅰ组治疗结束时肿瘤体积与Ⅳ组比较差异无统计学意义(P>0.05),Ⅱ、Ⅲ组的抑瘤率分别为63%和44%。结论131I标记高亲和融合多肽对荷人卵巢癌小鼠移植瘤的生长具有显著抑制作用。
Objective To observe the effect of targeted therapy with 131I-labeled affinity fusion polypeptide VEGF receptor 3 on human ovarian cancer transplanted into nude mice.Methods 131I-labeled polypeptide and anti-VEGFR-3 MAb were synthesized with Indogen method,cultured in vitro with LEC cells respectively,and their inhibitory effect on growth of LEC cells was detected by MTT.Human ovarian cancer cells were subcutaneously inoculated into 44 nude mice.Two weeks after tumor formation,20 mice were divided into polypeptide group （4.4 g per mouse）,131I-polypeptide group （7.4 MBq per mouse）,131I-anti-VEGFR-3 MAb （7.4 MBq per mouse）,and control group （0.2 ml saline）,5 mice in each group.The size of tumor was measured once a week for 4 weeks.Single photon emission computed tomography（SPECT）was performed when the tumor diameter reached 1cm in the other 24 mice.Results The in vitro inhibition rates of 131I-polypeptide and 131I-anti-VEGFR-3 MAb reached their peak in 72 and 96 h after treatment respectively （P0.05）.The in vivo tumor volume in the 4 groups was （723±164）,（291±68）,（457±88）,and （792±112）mm3,respectively,4 weeks after treatment,with a difference in 131I-polypeptide,131I-anti-VEGFR-3 MAb and control groups （P0.05） but no difference in polypeptide group and control group.The average volume of the tumor was significantly smaller in the 131I-polypeptide and 131I-VEGFR-3 MAb than in the control group（P0.05）.The growth of implanted tumor was inhibited by 63% and 44%,respectively.Conclusion 131I-labeled high affinity fusion polypeptide can significantly inhibit the growth of human ovarian cancer transplanted into mice.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2010年第9期891-894,共4页
Journal of Third Military Medical University
基金
国家自然科学基金(30371484)~~
