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ObjectiveTo evaluate the antitumor effects of chenodeoxycholic acid-verticinone ester (CDCA-Ver) on tumor growth and immune system of H22-bearing mice.MethodsAntitumor 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 chenodeoxycholic acid-verticinone 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 chenodeoxycholic acid-verticinone 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 chenodeoxycholic acid-verticinone.

Results chenodeoxycholic acid-verticinone (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.ConclusionCDCA-Ver treatment can significantly inhibit tumor growth in mice.


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