丹参酮ⅡA磺酸钠对MKN-45胃癌裸鼠移植瘤增殖及血管生成的影响  

Anticancer effects and mechanisms of Tanshinone ⅡA sulfonic acid in nude mouse xenograft model bearing MKN-45 gastric cancer cells

作　　者：陈坚[1] 钟良[1] 钱立平[1] 蒋蔚茹[1] 黄剑平[1] 邱冬妮[1] 

机构地区：[1]复旦大学附属华山医院消化科,上海市200040

出　　处：《世界华人消化杂志》2008年第22期2507-2511,共5页World Chinese Journal of Digestology

摘　　要：目的:明确丹参酮ⅡA磺酸钠(TanⅡA)在体内的抗癌作用及其对肿瘤血管生成的影响.方法:建立MKN-45胃癌裸鼠移植瘤模型,随机分成对照组和低、中、高丹参酮ⅡA磺酸钠干预组,每组6只.干预组分别用TanⅡA磺酸钠1、5、10mg/kg,ip,1次/d,连续14d.对照组等量生理盐水干预.2wk后处死裸鼠,分离瘤块,观察抑瘤率;TUNEL法测凋亡指数;CD34标志法观察四组瘤块微血管密度(MVD);免疫组化法观察缺氧诱导因子HIF1α、血管内皮生长因子(VEGF)、COX2的蛋白表达.结果:与对照组相比,3组干预组凋亡指数AI明显上升(36.02%±3.41%,34.78%±3.41%,30.05%±3.41%vs10.83%±0.92%,均P<0.05).低剂量组增殖减慢,抑瘤率为20.69%±1.79%;中、高剂量瘤重反而增加,高剂量组抑瘤率为-(21.4%±2.38%).与对照相比,3组干预组MVD、VEGF表达上调,尤以中高剂量组差异显著(8.11±1.011,10.01±0.89vs6.56±0.42;63628±611,70957±684vs51056±410,均P<0.05);3组干预组COX-2表达与对照无明显差异;HIF1α在低剂量组表达略有下调,但未达到统计学差异,中高剂量组表达则有明显上调(29468±204,42227±214vs15691±106,P<0.01或0.05).结论:丹参酮ⅡA体内的抗肿瘤效果没有体外细胞实验显著,高剂量丹参酮ⅡA的抗癌效应可被HIF的代偿高表达抵消甚至逆转.AIM： To identify the anticancer effects of Tanshinon Ⅱ A sulfonic acid （TASA） in vivo by the model of nude mice with MKN-45 gastric cancer cells transplanted subcutaneously. METHODS： MKN-45 human gastric cancer ceils were grown as xenografts in 24 immunodeficient mice, which were randomly divided into 4 groups. The mice in observation groups were injected intraperitoneally with TASA at 1 mg/kg （low dosage）, 5 mg/kg （median dosage） or 10 mg/kg （large dosage） once per day respectively for 2 wk while the mice in the fourth group were injected with sodium chloride as controls. All the nude mice were sacrificed 2 wk later and growth inhibition rates of transplanted tumors were measured by weighing the masses. Apoptosis index was tested by TUNEL assay. Microvascular density （MVD） was marked by CD34 staining. The protein expression levels of hypoxia-inducible factor 1alpha （HIF1α）, vascular endothelial growth factor （VEGF） and cyclooxygenase-2 （COX-2） were measured by immunohistochemistry. RESULTS： Compared with that in the control group, the apoptosis index was significantly increased in the three observation groups （36.02% ± 3.41%, 34.78% ± 3.41%, 30.05% ± 3.41% vs 10.83% ± 0.92%, all P 〈 0.05）. Low-dose TASA suppressed MKN-45 cell proliferation, and the growth inhibition rate was 20.69% ± 1.79%. On the contrary, median- and large-dose TASA promoted the growth of MKN-45 cells, and the growth inhibition rate in large-dose group was -（21.4% ± 2.38%）. Compared with that in the control group, MVD and VEGF expression were up-regulated in the observed groups, especially in the median- and large-dose group （8.11 ± 1.011, 10.01 ± 0.89 vs 6.56 ± 0.42; 63628 ± 611, 70957 ± 684 vs 51056 ± 410; all P 〈 0.05）. COX-2 expression had no significant difference between the four groups. HIF1α expression was slightly down-regulated in low-dose TASA group, not significantly; however, it was significantly upregulated in the median- and large-dose groups as compared with

关 键 词：丹参酮ⅡA 胃癌 裸鼠 缺氧诱导因子1Α TUNEL法 免疫组化 微血管密度 血管内皮生长因子 环氧合酶-2 

分 类 号：R735.2[医药卫生—肿瘤]