The inhibitory mechanism of evodialine in mice with cervical cancer transplantation
Objective To investigate the inhibitory effect of evodiamine(Evo)on transplanted tumor in mice with cervical cancer and its effects on mammalian target of rapamycin(mTOR)/p70 ribosomal protein S6 kinase(p70S6K)pathway.Methods Among 40 BALB/c nude mice,10 were randomly used as healthy group,and the rest were used to establish cervical cancer xenograft model.Thirty mice were successfully modeled and randomly divided into tumor-bearing group,Evo group,and Evo combined with lysophosphatidic acid(LPA)group,each with 10 rats.The mice in the Evo combined LPA group were given Evo(18 mg·kg-1)intragastrically and LPA(0.8 μmol·kg-1)was injected into the tail vein.The mice in the Evo group were administered with Evo(18 mg·kg-1)intragastrically,and an equal volume of normal saline was injected into the tail vein.The mice in healthy group and tumor-bearing group were given an equal volume of dimethyl sulfoxide(DMSO)by intragastric administration,and an equal volume of normal saline was injected into the tail vein.Once a day,the intervention lasted for 30 days.The tumor volume was measured.Flow cytometry was used to detect the proportion of CD4+and CD8+T lymphocytes in peripheral blood.Tunel staining was used to detect the apoptosis rate of transplanted tumor cells.Western blot method was used to detect the protein expression of mTOR,p-mTOR,p70S6K,and p-p70S6K in transplanted tumor tissues.Results Compared with the tumor-bearing group,the tumor volumes were decreased on the 10th,20th,and 30th day after intervention,the proportions of CD4+T lymphocytes,CD4+/CD8+ratio were increased,and the proportions of CD8+T lymphocytes,p-mTOR/mTOR,p-p70S6K/p70S6K were decreased in the Evo group(P<0.05).Compared with the Evo group,the tumor volumes were increased on the 10th,20th,and 30th day after intervention,the proportions of CD4+T lymphocytes,CD4+/CD8+ratio were decreased,and the proportions of CD8+T lymphocytes,p-mTOR/mTOR,p-p70S6K/p70S6K were increased in the Evo combined with LPA group(P<0.05).Conclusion Evo can inhibit the growth of cervical cancer transplantation tumors,promote the apoptosis of cervical cancer cells,and enhance the immune function in mice.Its mechanism may be related to the inhibition of mTOR/p70S6K signaling pathway.
evodiaminecervical cancermammalian target of rapamycinribosomal 40S small subunit S6K protein kinasesignaling pathway
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维普
