关键词: 5-fluorouracil Colon cancer Ginsenoside Rg3 Tumor angiogenesis Tumor growth

Mesh : Mice Animals Fluorouracil / therapeutic use Vascular Endothelial Growth Factor A / metabolism Angiogenesis Quality of Life Colonic Neoplasms Ginsenosides / pharmacology therapeutic use Neovascularization, Pathologic / drug therapy Necrosis / drug therapy Cell Line, Tumor

来  源:   DOI:10.12182/20240160506   PDF(Pubmed)

Abstract:
UNASSIGNED: To evaluate the inhibitory effect of ginsenoside Rg3 combined with 5-fluorouracil (5-FU) on tumor angiogenesis and tumor growth in colon cancer in mice.
UNASSIGNED: CT26 mouse model of colon cancer was established and the mice were randomly assigned to the control group, the ginsenoside Rg3 group, the 5-FU group, and the Rg3 combined with 5-FU group. The 5-FU group was injected intraperitoneally at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 10 days. Treatment for the Rg3 group was given at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 21 days via gastric gavage. The dose and the mode of treatment for the Rg3+5-FU combination group were the same as those for the 5-FU and the Rg3 group. The control group was intraperitoneally injected with 0.2 mL/d of normal saline for 10 days. The expression of vascular endothelial growth factor (VEGF) and CD31 and the microvascular density (MVD) of the tumor tissues were examined by immunohistochemistry. The blood flow signals and tumor necrosis were examined by color Doppler flow imaging (CDFI). The quality of life, survival rate, tumor volume, tumor mass, and tumor inhibition rate of the mice were monitored.
UNASSIGNED: After 21 days of treatment, the tumor volume and the tumor mass of all treatment groups were significantly decreased compared with those the control group, with the combination treatment group exhibiting the most significant decrease. The tumor inhibition rates of the Rg3 group, the 5-FU group, and the combination group were 29.96%, 68.78%, and 73.42%, respectively. Rg3 treatment alone had inhibitory effect on tumor growth to a certain degree, while 5-FU treatment alone or 5-FU combined with Rg3 had a stronger inhibitory effect on tumor growth. The tumor inhibition rate of the combination group was higher than that of the 5-FU group, but the difference was not statistically significant (P>0.05). Color Doppler ultrasound showed that there were multiple localized and large tumor necrotic areas that were obvious and observable in the Rg3 group and the combination group, and that there were only small tumor necrotic areas in the 5-FU group and the control group. The tumor necrosis rate of the combination group was (55.63±3.12)%, which was significantly higher than those of the other groups (P<0.05). CDFI examination of the blood flow inside of the tumor of the mice showed that the blood flow signals in the combination group were mostly grade 0-Ⅰ, and that the blood flow signals in the control group were the most abundant, being mostly grade Ⅱ-Ⅲ. The abundance of the blood flow signals in the Rg3 and 5-FU groups were between those of the control group and the combination group. Compared with those of the control group, the expression levels of MVD and VEGF in the tumor tissues of the Rg3 group, the 5-FU group, and the combination group were significantly decreased, with the combination group showing the most significant decrease (P<0.05). HE staining results indicated that there was significant tumor necrosis in mice in the control group and that there were more blood vessels. In contrast, in the tumor of the Rg3 group and the 5-FU group, there were fewer blood vessels and necrotic gaps appeared within the tumors. In the combination group, the tumor tissues had the fewest blood vessels and rope-like necrosis was observed. The mice started dying on the 18th day after treatment started, and all the mice in the control group died on the 42nd day. By this time, there were 3, 5, and 7 mice still alive in the Rg3 group, the 5-FU group, and the combination group, respectively, presenting a survival rate of 30%, 50%, and 70%, respectively. All mice in all the groups died on day 60 after treatment started.
UNASSIGNED: Ginsenoside Rg3 combined with 5-FU can significantly inhibit tumor angiogenesis and tumor growth of colon cancer in mice and improve the survival and quality of life of tumor-bearing mice.
摘要:
评价人参皂苷Rg3联合5-氟尿嘧啶(5-FU)对小鼠结肠癌肿瘤血管生成和肿瘤生长的抑制作用。
建立结肠癌CT26小鼠模型,将小鼠随机分配到对照组,人参皂苷Rg3组,5-FU集团,Rg3联合5-FU组。5-FU组腹腔注射20mg/kg,0.2毫升/只动物,每天一次,持续10天。Rg3组的治疗剂量为20mg/kg,0.2毫升/只动物,每天一次,持续21天。Rg3+5-FU组合组的剂量和治疗方式与5-FU和Rg3组的相同。对照组腹腔注射生理盐水0.2mL/d,连续10天。免疫组化法检测肿瘤组织中血管内皮生长因子(VEGF)和CD31的表达及微血管密度(MVD)。彩色多普勒血流显像(CDFI)检查血流信号及肿瘤坏死。生活的质量,存活率,肿瘤体积,肿瘤块,监测小鼠的抑瘤率。
治疗21天后,与对照组相比,各治疗组肿瘤体积和肿瘤质量均明显下降,联合治疗组表现出最显著的下降。Rg3组的肿瘤抑制率,5-FU集团,联合用药组为29.96%,68.78%,73.42%,分别。Rg3单独治疗对肿瘤生长有一定的抑制作用,而5-FU单独治疗或5-FU联合Rg3对肿瘤生长的抑制作用更强。联合用药组的抑瘤率高于5-FU组,但差异无统计学意义(P>0.05)。彩色多普勒超声显示,Rg3组及联合组均有较明显和可观察到的多个局部和较大的肿瘤坏死区,5-FU组和对照组仅有小的肿瘤坏死区。联合组肿瘤坏死率为(55.63±3.12)%,显著高于其他组(P<0.05)。CDFI检测小鼠肿瘤内血流信号显示,联合组血流信号多为0-Ⅰ级,对照组的血流信号最丰富,大多为Ⅱ-Ⅲ级。Rg3和5-FU组的血流信号丰度介于对照组和联合组之间。与对照组相比,Rg3组肿瘤组织中MVD和VEGF的表达水平,5-FU集团,联合组显着下降,联合组下降最显著(P<0.05)。HE染色结果表明,对照组小鼠肿瘤坏死明显,血管较多。相比之下,在Rg3组和5-FU组的肿瘤中,肿瘤内血管减少,坏死间隙出现。在组合组中,肿瘤组织的血管最少,观察到绳状坏死。老鼠在治疗开始后的第18天开始死亡,对照组的所有小鼠都在第42天死亡。到这个时候,在Rg3组中有3、5和7只小鼠仍然存活,5-FU集团,和组合组,分别,存活率为30%,50%,70%,分别。所有组中的所有小鼠在治疗开始后第60天死亡。
人参皂苷Rg3联合5-FU可以显著抑制小鼠结肠癌的肿瘤血管生成和肿瘤生长,提高荷瘤小鼠的生存和生活质量。
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