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目的研究血管形成抑制剂3TSR对裸鼠皮下胆囊癌种植瘤的抑制作用及其机制。方法建立裸鼠皮下胆囊癌种植瘤模型,进行随机干预实验,实验分为对照组、3TSR组、5-氟尿嘧啶(5-FU)组和3TSR+5-FU组,每组6只。检测荷瘤体积、胆囊癌细胞增殖指数(PCNA)、凋亡率、微血管密度(MVD)、肿瘤血管内皮细胞凋亡率及血管内皮生成因子(VEGF)的表达。结果(1)3TSR组、5-FU组和3TSR+5-FU组肿瘤体积较对照组显著减小,分别缩小31.1%,38.3%和60.2%。对照组、3TSR组、5-FU组和3TSR+5-FU组胆囊癌细胞增殖指数分别为(25.8±2.4)%,(23.7±5.0)%,(9.4±2.5)%和(11.9±3.8)%,其中3TSR组增殖指数与对照组比较无显著差异,但5-FU组和3TSR+5-FU组细胞增殖指数显著小于对照组和3TSR组(P<0.05)。4组胆囊癌细胞凋亡率分别为(5.1±1.4)%,(4.3±1.6)%,(19.8±5.1)%和(13.9±3.8)%,其中3TSR组胆囊癌细胞凋亡率与对照组比较无显著差异(P<0.05),但5-FU组和3TSR+5-FU组细胞凋亡率显著大于对照组和3TSR组(P<0.05)。4组微血管密度分别为(15.2±4,6)%,(4.2±1.2)%,(8.7±2.1)%和(4.9±1.8)%,其中含3TSR的两组显著低于对照组和5-FU组(P<0.05)。4组内皮细胞凋亡率分别为(4.3±1.4)%,(10.8±2.9)%,(5.1±2.1)%和(10.2±3.0)%,其中含3TSR组显著高于对照组(P<0.05)。4组VEGF表达率分别为(14.0±3.2)%,(4.7±2.8)%,(12.8±1.4)%和(6.7±2.9)%,其中含3TSR的两组显著低于对照组和5-FU组(P<0.05)。结论3TSR显著减少肿瘤体积,抑制微血管生成.其机制可能与诱导内皮细胞凋亡和抑制VEGF有关;3TSR与化疗药物5-FU合用对胆囊癌的治疗有协同作用。本研究为3TSR的临床前期应用提供了一定实验基础。
Objective To study the inhibitory effect of 3TSR, an angiogenesis inhibitor, on the implanted tumor of subcutaneous gallbladder carcinoma in nude mice and its mechanism. Methods The implanted tumor model of subcutaneous gallbladder carcinoma in nude mice was established and randomly divided into control group, 3TSR group, 5-fluorouracil group and 3TSR + 5-FU group, with 6 rats in each group. The tumor volume, gallbladder cancer cell proliferation index (PCNA), apoptotic rate, microvessel density (MVD), tumor vascular endothelial cell apoptosis rate and the expression of vascular endothelial growth factor (VEGF) were detected. Results (1) The tumor volume of 3TSR group, 5-FU group and 3TSR + 5-FU group was significantly reduced compared with that of control group, which were reduced by 31.1%, 38.3% and 60.2% respectively. The proliferative index of gallbladder carcinoma cells in control group, 3TSR group, 5-FU group and 3TSR + 5-FU group were (25.8 ± 2.4)%, (23.7 ± 5.0)%, (9.4 ± 2.5)% and (11.9 ± 3.8) %. The proliferation index of 3TSR group was not significantly different from that of control group, but the proliferation index of 5-FU group and 3TSR + 5-FU group was significantly lower than that of control group and 3TSR group (P <0.05). The apoptotic rates of gallbladder carcinoma in the three groups were (5.1 ± 1.4)%, (4.3 ± 1.6)%, (19.8 ± 5.1)% and (13.9 ± 3.8)%, respectively. (P <0.05). However, the apoptosis rates in 5-FU group and 3TSR + 5-FU group were significantly higher than those in control group and 3TSR group (P <0.05). The microvessel density in the 4 groups were (15.2 ± 4,6)%, (4.2 ± 1.2)%, (8.7 ± 2.1)% and (4.9 ± 1.8)%, respectively. FU group (P <0.05). The apoptotic rates of endothelial cells in the 4 groups were (4.3 ± 1.4)%, (10.8 ± 2.9)%, (5.1 ± 2.1)% and (10.2 ± 3.0)%, respectively ). The VEGF expression rates in the 4 groups were (14.0 ± 3.2)%, (4.7 ± 2.8)%, (12.8 ± 1.4)% and (6.7 ± 2.9)%, respectively Group (P <0.05). Conclusions 3TSR can significantly reduce tumor volume and inhibit angiogenesis, which may be related to the induction of endothelial cell apoptosis and VEGF inhibition. 3TSR and 5-FU chemotherapeutic drugs have synergistic effects on the treatment of gallbladder cancer. This study provided a certain experimental basis for the clinical application of 3TSR.