目的:探讨胞浆活化T细胞核因子1(nuclear factor of activated T-cells,cytplasmic 1,NFATc1)对人卵巢癌SKOV3细胞裸鼠移植瘤生长和肿瘤脉管生成的影响及其可能机制。方法:NFATc1 si RNA转染人上皮性卵巢癌细胞株SKOV3,免疫荧光及RT-PC...目的:探讨胞浆活化T细胞核因子1(nuclear factor of activated T-cells,cytplasmic 1,NFATc1)对人卵巢癌SKOV3细胞裸鼠移植瘤生长和肿瘤脉管生成的影响及其可能机制。方法:NFATc1 si RNA转染人上皮性卵巢癌细胞株SKOV3,免疫荧光及RT-PCR测量转染效率和基因抑制率,选取效率最高的序列建立裸鼠皮下移植瘤模型,测量各组裸鼠肿瘤体积,观察NFATc1 siRNA的体内抗肿瘤作用。免疫组织化学检测各组肿瘤组织NFATc1的表达情况,并使用细胞角蛋白染色标记上皮性来源,CD34标记微血管,podoplanin标记微淋巴管。分别计算各组微血管及微淋巴管密度并进行统计学分析。应用RT-PCR及Western blot检测各组移植瘤组织NFATc1、CXC趋化因子受体2(CXCR2)、成纤维细胞生长因子2(FGF-2)及血小板源性生长因子BB(PDGF-BB)的mRNA及蛋白表达水平。结果:3条特异性序列均可显著降低NFATc1的表达水平,以siRNA-1169最佳。NFATc1在空白组及阴性对照组瘤组织高表达。干扰组抑瘤率为57.08%,且重量和体积均低于2个对照组。空白组和阴性对照组的微血管密度和微淋巴管密度明显高于干扰组。对照组比较,NFATc1 siRNA可以在mRNA水平上明显抑制NFATC1、CXCR2、FGF-2和PDGF-BB的转录。Western blot各组细胞在相应位置出现NFATc1、CXCR2、FGF-2和PDGF-BB条带,空白组与阴性对照组的吸光度最强,与干扰组比较具有显著差异。结论:NFATc1 siRNA明显抑制人卵巢癌SKOV3细胞裸鼠皮下移植瘤生长和肿瘤脉管生成,下调CXCR2、FGF-2及PDGF-BB的表达可能为其途径之一。展开更多
AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the ...AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg·d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2±12.7 μmol/L Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89±32.07 mm3) compared to the control group (828.21±31.59 mm3) (P<0.05). The MVD of the treated group (19.50±5.32) was markedly decreased compared to the control group (37.40±4.93) (P<0.001). The VEGF expression of the treated group (1.19±0.17) was obviously reduced as compared to the control group (1.90±0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (rs = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.展开更多
基金Supported by National Natural Science Foundation of China, No. 30271516
文摘AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg·d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2±12.7 μmol/L Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89±32.07 mm3) compared to the control group (828.21±31.59 mm3) (P<0.05). The MVD of the treated group (19.50±5.32) was markedly decreased compared to the control group (37.40±4.93) (P<0.001). The VEGF expression of the treated group (1.19±0.17) was obviously reduced as compared to the control group (1.90±0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (rs = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.
