鹅去氧胆酸浙贝乙素酯对H22荷瘤小鼠抑瘤作用

Inhibitory Effect of Chenodeoxycholic Acid-verticinone Ester on Tumor Growth of H22-bearing Mice

目的研究新型化合物鹅去氧胆酸浙贝乙素酯(CDCA-Ver)对H22荷瘤小鼠体内肿瘤细胞生长和免疫器官的影响。方法采用鼠系肝癌细胞H22造荷瘤模型,将H22荷瘤小鼠40只,采用随机数字表法随机分成4组,每组10只,分别为模型对照组、环磷酰胺(CTX)组、CDCA-Ver腹腔注射组和CDCA-Ver静脉注射组。模型对照组按每日10 m L·kg-1无菌0.9%氯化钠溶液腹腔注射1次,CTX组按每日20 mg·kg-1剂量腹腔注射1次,CDCA-Ver腹腔注射组每日按20 mg·kg-1剂量腹腔注射1次,CDCA-Ver静脉注射组每日按20 mg·kg-1剂量小鼠尾静脉注射1次。接种24 h后给药,给药量为0.1 m L·(10 g)-1,连续给药10 d。以CTX为阳性对照药,考察CDCA-Ver(静脉注射和腹腔注射)对荷瘤小鼠肿瘤的生长抑制作用,评价CDCA-Ver对荷瘤小鼠的免疫脏器指数(胸腺指数和脾指数)的影响,采用组织病理学切片法研究CDCA-Ver对荷瘤小鼠瘤块组织病理学形态的影响。结果 CDCA-Ver静脉注射和腹腔注射两种给药方式对荷瘤小鼠的肿瘤生长均具有良好的抑制作用,腹腔注射20 mg·kg-1剂量CDCA-Ver抑瘤率达48.3%,与模型对照组比较差异有统计学意义(P<0.05),与CTX组作用相当。与模型对照组相比,CDCA-Ver腹腔注射组脾指数和胸腺指数没有显著变化(P>0.05),而CTX组脾指数和胸腺指数均显著降低(P<0.01),表明CDCA-Ver发挥体内抗肿瘤作用不会降低荷瘤小鼠的免疫功能。组织病理学结果也证实CDCA-Ver具有体内抗肿瘤作用。结论 CDCA-Ver对H22荷瘤小鼠肿瘤生长具有明显的抑制作用。

Objective To evaluate the antitumor effects of chenodeoxycholic acid-verticinone ester （ CDCA-Ver ） on tumor growth and immune system of H22-bearing mice. Methods Antitumor activity against a solid tumor mass was evaluated in Kunming mice. H22 cells were transferred into the abdomen cavity of Kunming mice. H22 cells were inoculated through subcutaneous injection at the right armpit of the mouse to establish a solid tumor model. At 24 h after H22 tumor cells inoculation, 40 tumor-bearing Kunming mice were randomly divided into 4 groups according to random number table （ n=10 each group）：model control group, cyclophosphamide （ CTX） group, intraperitoneal CDCA-Ver injection group and intravenous CDCA-Ver injection group. In model control group, sterile 0. 9% sodium chloride solution （10 mL·kg-1 ） was intraperitoneally injected once daily. In CTX group and intraperitoneal CDCA-Ver injection group, CTX （20 mg·kg-1 ） and CDCA-Ver （20 mg·kg-1 ） was intraperitoneally injected once daily, respectively. In intravenous CDCA-Ver injection group, CDCA-Ver （ 20 mg · kg-1 ） was injected through tail vein once daily. CDCA-Ver, CTX and NS were injected into the mice of the experimental groups once daily for 10 days, respectively. The dose volume was 0. 1 mL · （ 10 g ）-1 body weight. The positive control drug was cyclophosphamide. Ten mice were treated with 20 mg · kg-1 CDCA-Ver through intravenous injection （ i. v. ） . Ten mice were treated with 20 mg·kg-1 CDCA-Ver through intraperitoneal injection. The thymus and spleen indices and the tumor inhibition rate were assessed, and histopathological examination with haematoxylin and eosin （ H＆E） staining was carried out to evaluate the antitumor effects of CDCA-Ver. Results CDCA-Ver （ ivor ip） suppressed the growth of solid tumor in H22-bearing mice. The inhibition rate was 48. 3% at the dose of 20 mg·kg-1 CDCA-Ver （ip）. There was no significant difference between CDCA-Ver （ip） and CTX treated group （P〈0. 05）. Compared with the control, the weight of thymus and spleen of CDCA-Ver （ip） treated group was not obviously changed. But a significant weight loss of thymus and spleen in CTX group was observed, which was attributed to the immune suppression from CTX. The thymus and spleen indices in the CTX-treated mice were significantly lower than those of the control group （P〈0. 01）. We further conducted histopathological examination to confirm the results. The immune system was not suppressed by CDCA-Ver （ ip ） in tumor-bearing animals. The low toxicity of CDCA-Ver was an outstanding advantage for the development of newly anticancer drug. Conclusion CDCA-Ver treatment can significantly inhibit tumor growth in mice.