摘要
目的:观察槲皮素联合苏拉明对肺腺癌LA795细胞的T739小鼠移植瘤生长的抑制作用,并探讨其作用机制。方法:将40只接种LA795肺腺癌细胞T739小鼠随机分成5组:A对照组、B顺铂组(DDP)、C槲皮素组、D苏拉明组、E槲皮素+苏拉明组。用药16d,观察药效、不良反应及肿瘤生长情况,于接种后24d处死各组小鼠,收集移植瘤标本行光镜观察,免疫组化和图像分析系统定量检测肿瘤组织微血管密度(MVD)、血管内皮生长因子(VEGF)及增殖核抗原(PCNA)的表达,原位凋亡TUNEL法检测肿瘤细胞凋亡指数。结果:①B、C、D、E各用药组肿瘤的生长明显受到抑制,瘤质量明显低于A组(P<0.05),其抑瘤率分别为23.03%、39.77%、34.40%、54.70%,联合用药组抑瘤作用明显者增强(P<0.01)。②光镜观察:B、C、E组肿瘤细胞出现坏死,D、E组肿瘤间质中血管数减少。③免疫组化:D、E组MVD值明显低于A、B、C组,各用药组都能减少VEGF、PCNA表达,与对照组相比均具有差异显著性;各用药组的凋亡指数都比对照组明显提高(P<0.01)。④不良反应:B组有不良反应。结论:槲皮素联合苏拉明可明显抑制肺腺癌细胞在小鼠体内的生长,其作用机制可能是抑制其微血管形成、抑制细胞增殖和促进细胞凋亡。
Objectlve：To study the effect of quercetin in combination with suramin on growth of transplanted lung adenocarcinoma in mice and corresponding mechanism. Methods： Forty T739 mice bearing LA795 lung adenocarcinoma cells were randomly divided into five groups： （A） control group; （B） cis-dichlorodiammineplatinum （DDP） group; （C） quereetin group; （D） suramin group; （E） quercetin＋suramin group. Different treatments were served from day 4 after transplantation of tumor ceils and the drug effect, adverse reaction,and growth of transplanted tumors were observed at d 16 after drug treatment. The volumes of tumors in different groups were measured during the therapeutic period, respeetively. All the mice were sacrificed at d 24 after transplantation. Subcutaneous tumors were subjected to histological examination. The microvessel density （MVD） and the expression of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （PCNA） in tumor tissues were de retted hy immunohistochemistry using image analysis system. Apoptoais of tumor cells was measured by biotinylated dUTP nick end labeling （TUNEL） method. Results： 1）In every treatment group tumor growth was suppressed significantly. Intraperitoneal injection of DDP, quercetin, suramin, and quercetin ＋ suramin resulted in a significant inhibition of the growth of LA795 ceils in viw;compared with control group（P〈0.05）. The inhibition rate was 23.0%, 39.77%, 34.40%, and 54.7%, respectively. The anti-tumor efficacy of quercctin plus suramin was significantly enhanced compared with quereetin or suramin treatment alone. 2）Light microscopy. Tumor necrosis was observed in DDP, quercetin and quercetin ＋ suramin group. The number of ves sels in the tumor tissues was rcduced in suramin and qucreetin ＋ suramin group. 3）Immunohistoehemistry. MVD of surarnin group and quercetin ＋ suramin group was markedly lower than that of control, DDP, and ttuercetin group. Expression of VEGF and PCNA decreased in every treatment group. The difference was significant compared with control. Apoptotic index increased in every treatment group compared with control. 4） Adverse reaetion, control ,quercetin, suramin, quercetin＋suramin group did not show significant adverse reaction, while DDP group showed some adverse reactions. Conclusion： Quercetin combined with suramin can significantly inhibit the growth of transplanted lung adenocarcinoma in mice in viva by induction of apoptosis and inhibition of angiogenesis and eell proliferation.
出处
《肿瘤》
CAS
CSCD
北大核心
2006年第4期322-326,共5页
Tumor
基金
湖南省卫生厅科研基金资助项目(编号:C2005033)
关键词
肺肿瘤
腺癌
槲曳素
苏拉明
血管生成抑制药
肿瘤移植
动物
Lung neoplasms
Adenocarcinoma
Quercetin
Suramin
Angiogenesis inhibitors
Neoplasm transplatation,
