摘要
目的:评价超分子药物西茜铂实验性治疗消化系肿瘤的效果.方法:用细胞培养方法测定西茜铂和卡铂对肝癌(BEL7402),胰腺癌(BXCP-3,JF305),胃癌(MG803,SG7901)和结肠癌(CX-1)6株消化系癌细胞株和一株人胚胎肺成纤维细胞的半数抑制浓度(IC_(50)).建立肝癌H22昆明鼠模型和人胰腺癌JF305裸鼠模型,腹腔注射高(20 mg/ kg)、中(15 mg/kg)、低(10 mg/kg)剂量西茜铂,测定其在动物体内的抑瘤作用,注射葡萄糖注射液作为阴性对照,注射20 mg/kg卡铂作为阳性对照.HE染色判断肿瘤组织的坏死.CD34抗体免疫组化染色观察肿瘤组织中微血管的生长状况.结果:西茜铂对6株肿瘤细胞的IC_(50)值明显低于卡铂,约为后者1/3至1/2.但2种药物对人胚胎肺成纤维细胞的半数抑制浓度(IC_(50))均大于240 mg/L.在肝癌H22荷瘤昆明小鼠,腹腔注射高、中、低剂量西茜铂的抑瘤率分别为56.1%-67.0%,46.9%-54.8%和42.4%-44.3%,卡铂的抑瘤率是50.3%-51.3%.西茜铂和卡铂治疗组的瘤质量与葡萄糖组相比,明显降低(t>2.91,P<0.01).20 mg/kg西茜铂的抑瘤率高于相同剂量卡铂的抑瘤率,瘤质量均值也明显轻于卡铂组(t=2.39,P<0.05).在接种人胰腺癌JF305裸鼠,高、中、低剂量西茜铂组的抑瘤率分别为61.4%-73.4%,51.4%-54.0%和17.6%-22.6%,卡铂的抑瘤率是37.1%-42.0%.中、高剂量的抑瘤率明显高于卡铂组,瘤质量明显低于葡萄糖组和卡铂组(t>2.28,P<0.05).经HE染色后,在接种人胰腺癌JF305裸鼠,西茜铂治疗组的瘤组织见大片出血性坏死.CD34抗体免疫组化染色在葡萄糖组可见有大量的微血管形成,而西茜铂治疗组仅有少数微血管生成,微血管生成受到抑制.结论:超分子药物西茜铂对消化系统肿瘤有明显的抑制作用,其作用明显高于卡铂.
AIM: To investigate in vivo and in vitro inhibitory effects of a supramolecular drug-platinum compound CCP on digestive tumors. METHODS: Six digestive tumor cell lines, hepatocellular carcinoma (BEL7402), gastric carcinoma (MG803 and SG7901), pancreatic carcinoma (BXCP-3 and JF305), and colon carcinoma (CX-1), were used to test the ICs0 of CCP and carboplatin. H22-bearing Kunming mice and JE305-bearing nude mice were treated intraperitoneally with CCP at 10, 15 or 20 mg/kg. Mice were treated with glucose as a negative control and carboplatin as a positive control. HE stain- ing was used to detect tumor necrosis, and CD34 antibody was used to demonstrate differences in microvasculature in tumors. RESULTS: The IC50 of CCP was only 33% - 50% of that of carboplatin. The ICs0 of both CCP and carboplatin was 〉 240 mg/L in lung embryo fibroblasts. In H22-bearing Kunming mice, the inhibitory rate for 20, 15 and 10 mg/kg CCP was 56.1% - 67.0%, 46.9% - 54.8% and 42.4% - 44.3%, respectively, and the inhibitory rate for CBP was 50.3% - 51.3%. Tumor weight in the CCP group was lower than that in the control group (t 〉 2.91, P 〈 0.01). In the CCP 20 mg/kg group, the inhibitory rate for CCP was higher and the tumor weight was lower than those in the carboplatin group (t = 2.39, P 〈 0.05). In JF305-bearing nude mice, the inhibitory rate for 20 and 15 mg/kg CCP was 61.4% - 73.4% and 51.4% - 54.0%, respectively, and the inhibitory rate for carboplatin was 37.1%-42.0%. Tumor weight was significantly lower than that in the control groups (t 〉 2.28, P 〈 0.05). However, the inhibitory rate of 10 mg/kg CCP was 17.6% - 22.6%, which was not different from that in the glucose group (t = 1.70). The microvascular growth in JE305-bearing nude mice showed more necrosis in the CCP group with HE staining. Immunohistochemical staining with anti-CD34 antibody suggested more microvascular formation in the glucose group, but it was more clearly inhibited in the CCP group. CONCLUSION: CCP has a greater ability to inhibit digestive tumor growth than carboplatin.
出处
《世界华人消化杂志》
CAS
北大核心
2007年第33期3489-3494,共6页
World Chinese Journal of Digestology
基金
教育部归国博士启动课题
No.2004-527
No.2004-231~~
关键词
消化系统
肿瘤
西茜铂
卡铂
Digestive system tumor
CCP
Carboplatin