六味地黄丸抑制移植性原发性肝癌小鼠肿瘤生长的实验研究

Experimental study of Liuwei- dihuang pill on inhibition of tumor growth in mice with transplanted primary liver cancer

目的观察六味地黄丸对移植性原发性肝癌(以下简称肝癌)小鼠肿瘤生长的影响,探讨其作用机制。方法将30只移植性肝癌模型小鼠随机分为模型组、实验组及氟尿嘧啶注射液(5-FU)组,每组10只。模型组和实验组小鼠分别予蒸馏水和六味地黄丸汤剂灌胃,每日1次,连续灌胃10 d;5-FU组予5-FU腹腔注射,隔日1次,治疗10 d。观察各组小鼠肿瘤表观扩散系数(ADC)、血清血管内皮生长因子(VEGF)、体质量、去瘤体质量、肿瘤质量、肿瘤指数、肿瘤生长抑制率(抑瘤率)、肿瘤细胞凋亡及肿瘤细胞周期的情况变化。结果造模后第8 d,实验组小鼠体质量均高于5-FU组及模型组(P<0.05),5-FU组与模型组体质量相当(P>0.05);造模后第16 d,实验组及5-FU组小鼠体质量及去瘤体质量均高于模型组(P<0.05),且实验组比5-FU组高出更明显(P<0.05)。各组小鼠肿瘤质量及肿瘤指数比较,实验组均低于模型组(P<0.05),均高于5-FU组(P<0.05),各组组间比较差异均有统计学意义(P<0.05)。实验组与5-FU组抑瘤率比较,实验组低于5-FU组(P<0.05)。各组小鼠肿瘤细胞凋亡百分比比较,实验组高于模型组(P<0.05),低于5-FU组(P<0.05),各组组间比较差异均有统计学意义(P<0.05)。各组小鼠细胞周期百分比比较,实验组G0-G1期细胞高于模型组(P<0.05),低于5-FU组(P<0.05),各组组间比较差异均有统计学意义(P<0.05);实验组S期细胞高于5-FU组(P<0.05),与模型组相当(P>0.05);各组G2-M期细胞组间比较差异均无统计学意义(P>0.05)。各组小鼠血清VEGF水平及ADC值比较,实验组均低于模型组(P<0.05),均高于5-FU组(P<0.05),各组组间比较差异均有统计学意义(P<0.05)。结论六味地黄丸可明显抑制肝癌小鼠瘤体生长,影响瘤体细胞周期,诱导小鼠肝癌细胞凋亡,降低血清VEGF水平,降低肿瘤ADC值,从而产生良好的抗肿瘤作用。

Objective To observe the effect of Liuwei - dihuang pill on tumor growth in mice with trans- planted primary liver cancer, and to explore the mechanism. Methods 30 mice with transplanted primary liver cancer were randomly divided into model group, experimental group and fluorouracil injection （5 - FU ） group, 10 mice in each group. Mice in model and experimental group were received distilled water and Liuwei- dihuang - pill decoction by gavage respectively once a day for 10 days. Mice in 5 - FU group were injected with 5 - FU in cavity once every other day for 10 days. The tumor apparent diffusion coefficient （ADC）, vascular endothelial growth factor （VEGF）, body mass, body mass withotlt tumor, tumor mass, tumor index, tumor growth inhibition rate, tumor cell apoptosis and tumor cell cycle were observed in three group. Results Eight days after modeling, the mice body mass in experimental group was higher than that in 5 - FU and model group （ P 〈 0.05 ）. Mice body mass in 5 - FU group was equivalent to that in model group （P 〈 0.05 ）. 16 days after modeling, the body mass and body mass without tumor in experimental and 5 - FU group were higher than those in model group （P 〈 0. 05 ）, and the increased in experimental group was more obviously as compared with that in 5 - FU group （P 〈 0.05 ）. The tumor mass and tumor index in experimental group were lower than those in model group （ P 〈 0.05 ） , but higher than 5 - FU group （ P 〈 0. 05 ） , with statistical significance （ P 〈 0.05 ）. The tumor growth inhibition rate in experimental group was lower than that in 5 - FU group （ P 〈 0.05 ）. The percentage of tumor cell apoptosis in experimental group was higher than that in model group （ P 〈 0.05 ）, and lower than that in 5 - FU group （ P 〈 0.05 ）, there was statistically significant differ- ence among three group （P 〈0.05）. The percentage of tumor cell cycle in experimental group with stage GO to G1 was higher than that in model group （ P 〈 0.05）, and lower than that in 5 - FU group （ P 〈 0.05）, there was statisti- cally significant difference among three group （ P 〈 0.05 ）. The number of stage S cell in experimental group was high- er than that in 5 - FU group （ P 〈 0.05 ）, and equivalent to that in model group （ P 〈 0.05 ）. There was no statistical- ly significant difference on stage G2 - M cell among three groups （ P 〉 0.05 ）. The levels of serum VEGF and ADC in experimental group were lower than those in model group （ P 〈 0.05 ）, and higher than those in 5 - FU group （ P 〈 0. 05 ） , there was statistically significant difference on stage G2 - M cell among three group （ P 〈 0.05 ）. Conclusion Liuwei -dihuang pill can significantly inhibit the tumor growth in liver cancer mice, affect the tumor cell cycle, induce mice liver cancer cell to apoptosis, decrease serum VEGF level, decreased ADC level of tumor, thus produce good antitumor effect.