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烟曲霉醇联合5-氟尿嘧啶对SCID鼠胃癌生长的影响及机制研究 被引量:1

Influence of TNP-470 in Combination With 5-FU on the Growth of Gastric Cancer and its Mechanism Involved in SCID Mice
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摘要 目的探讨血管生成抑制剂烟曲霉醇(TNP-470)联合5-氟尿嘧啶(5-FU)对胃癌生长的影响及相关机制。方法完整组织块SCID鼠胃壁原位种植,建立胃癌模型。将荷瘤小鼠48只随机分成4组:对照组、5-FU组、TNP-470组和联合组,每组12只。移植后第7天开始,分别自腹腔注射生理盐水(对照组)、5-FU(5-FU组)、TNP-470(TNP-470组)、5-FU和TNP-470联合用药(联合组),每日1次,共6周。种植后第8周末处死动物,原位肿瘤切除称重,计算抑瘤率及q值,采用免疫组化半定量检测肿瘤组织微血管密度(MVD)及血管内皮生长因子(VEGF)表达水平,用TUNEL法检测肿瘤细胞凋亡指数(AI)。结果5-FU组、TNP-470组以及联合组肿瘤的生长明显受到抑制,瘤重明显低于对照组(P<0.05),其抑瘤率分别为35.1%、44.8%、73.3%,联合组抑瘤率明显高于5-FU组及TNP-470组(P<0.05),q=1.16。TNP-470组和联合组MVD、VEGF表达水平明显低于对照组,差异有显著性(P<0.05),而5-FU对MVD及VEGF表达无明显影响。各用药组AI较对照组显著增高,以联合组最高(P<0.05)。结论TNP-470对胃癌生长有明显抑制作用,与5-FU联用可起协同作用,其机制可能与抑制微血管形成和促进细胞凋亡有关。 Objective To explore the influence of TNP - 470 in combination with 5 - FU on the growth of gastric cancer in SCID mice and its mechanism. Methods Metastatic mode was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Forty - eight mice were randomly divided into 4 groups: control group, 5- FU group, TNP- 470 group and combination group. There are 12 mice in every group. Saline,5 - FU,TNP - 470 and 5 - FU plus TNP - 470 were administered by i.p. every day for 6 weeks after tumor implantation. All mice were sacrificed and tumor weight, tumor inhibitory rates and q value were computed. The microvessel density (MVD) and expression levels of vascular endothelial growth factor (VEGF) were detected by immunhistocheinical method. The apoptosis index (AI) was measured by TUNEL. Results The tumor growth was suppressed significandy in 5 - FU, TNP - 470 and combination groups and their tumor weights were markedly decreased compared with control group. 5 - FU, TNP - 470 and combination had a growth inhibition rate of 35.1% ,44.8% and 73.3% respectively. The q value was 1.16.The expression levels of VEGF and MVD were significantly lower in TNP- 470, combination groups than control group, however 5 - FU had no obvious influence on them. AI was enhanced in 5 - FU,TNP - 470 and combination groups compared with control group. Conclusion TNP - 470 has a strong inhibitory effect on tumor growth of human gastric cancer transplanted in SCID mice, and has synergetic inhibitory effect combined with 5 - FU through inhibiting microvessel angiogenesis and promoting cell apoptosis.
出处 《南华大学学报(医学版)》 2007年第6期826-828,855,共4页 Journal of Nanhua University(Medical Edition)
关键词 胃癌 烟曲霉醇 5-氟尿嘧啶 凋亡 gastric cancer TNP- 470 5 - FU apoptosis
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