重组纤粘连蛋白多肽CH50对小鼠H22肝癌移植瘤的治疗作用  

Therapeutic effects of recombinant fibronectin CH50 on transplantation tumor of mouse hepatoma H22.

作　　者：于智睿[1] 熊婷[1] 张书辰[2] 

机构地区：[1]华中科技大学同济医学院生物化学与分子生物学系,武汉430030 [2]华中科技大学同济医学院附属同济医院过敏反应科

出　　处：《华中医学杂志》2006年第4期304-306,共3页Central China Medical Journal

基　　金：国家重点基础研究发展(973)计划资助项目(No.2002CB513100)

摘　　要：目的探讨尾静脉转染CH50多肽真核表达载体pCH510对肿瘤的治疗作用及其可能的分子机制。方法尾静脉注射CH50多肽真核表达载体pCH510，RT-PCR检测该质粒在BALB／c小鼠肌肉和肝脏中的表达，以H22肝癌细胞接种于小鼠右后腿肌肉内，建立小鼠肝癌移植瘤模型，将小鼠分成3组，经尾静脉分别注射pCH510（C组）、pcDNA3．1（P组）和生理盐水（S组），肿瘤接种后第2天开始，每隔2天对小鼠进行治疗。HE染色观察治疗后肿瘤生长、侵袭和血管形成的改变。RT-PCR比较经CH50多肽处理的肿瘤细胞中口αv、β83和cdc2的mRNA表达。结果小鼠肌肉和肝脏内均可检测到CH50多肽的表达，持续表达48-72h。治疗后C组的小鼠移植肿瘤湿重为（0．80±0．18）g，小于P组的（1．75±0．23）g，也小于S组的（2．02±0．38）g，均有显著性差异（P〈0．05），P、S组间无显著性差异。CH50多肽治疗可抑制肿瘤细胞侵袭生长和肿瘤血管生成。CH50多肽可下调H22细胞的αv、β3、cdc2基因的表达水平。结论非定向转染表达CH50多肽有较好的肿瘤治疗作用，这可能与CH50多肽干扰了αvβ3的功能有关。Objective To investigate the therapeutic effect of transfection eucaryotic expressing plasmid of pCH510 through vena caudalis, in order to find out the possible mechanism of CH50 on tumor therapy. Methods Reverse transcription polymerase chain reaction （RT-PCR） was used to detect the mRNA expression of the CH50 in muscle and liver of BALB/c mice, which were transfected with pCH510 through vena caudalis. Transplantation tumor model was established by inoculation of H22 hepatocarcinoma cells at right hind thigh of mice. Beginning from the second day after inoculation, mice were divided into three groups, which were treated with pCH510 （group C）, pcDNA3. 1 （group P）, and sodium （group S） through venacaudalis respectively every two days. After treatment, the inhibitory effect on tumor growth, invasion and angiogenesis was observed by histotomy and HE straining of tumor tissues. RT-PCR were applied to evaluate the mRNA expression level of ανβ3 and cdc2 in tumor cells. Results The mRNA expression of CH50 can be detected in muscle and liver, which last at least 72 h. After treatment, tumor weight of group C was （0. 80 ＋ 0. 18）g, of group P was （1.75 ＋ 0. 23）g, of group S was （2. 02 ＋0. 38）g. in comparison among groups the mean weight of group C was significantly different from group P and group S （P〈 0. 05）, no significantly difference existed between group P and group S. Polypeptide CH50 could inhibit the growth, invasion and angiogenesis of tumor. The expression of αν,β3 and cdc2 mRNA in H22 cells treated with polypeptide CH50 was downregulated. Conclusian Non-targeting transfection polypeptide CH50 has significantly antitumor effect, which may be related with the down-regulation of expression and function of ανβ3.

关 键 词：肝肿瘤 实验性 CH50多肽 小鼠肝癌H22细胞 非定向转染 整合素ΑVΒ3 

分 类 号：R735.7[医药卫生—肿瘤] R730.5[医药卫生—临床医学]