Experimental Study On Growth Inhibition Of Medroxyprogesterone Acetate On Colonic Cancer Cells In Vitro And In Vivo

Objective: To study the effect of medroxyprogesterone acetate on human colonic cancer cells LS174-T growth in vitro and in vivo and its mechanisms. Methods: LS174T cells were cultured in the presence of MPA combined with chemotherapy drugs for 48 hours. The in vitro growth of LS174T cells was measured with MTT method and the cells cycle and cells surface Fas expression was analyzed with flow cytometry. RT-PCR was employed to detect the expression of Fas mRNA LS174T cells. LS174T cells were inoculated subcutaneously into 30 nude mice,which were then randomized equally into three groups: a MPA-treated group(B group,n=10) received 30 mg/kg/day MPA via gastrointestinal gavage and a MPA-treated group with 5-FU(C group,n=10) was administered at 30 mg/kg and a control group(A group,n=10).Three groups were treated five times a week for 3 weeks.After treatment ,the bulk of subcutaneous tumors was measured,and the cells cycle and cells surface Fas/FasL expression were analyzed with flow cytometry.and Fas/FasL were examined by immunohistochemical staining with anti-Fas/FasL antibody.Results: The proliferation of LS174T was inhibited by MPA in a dose- and time-manner.There were more cells arrested in G₁/G₀ phase and the exoression of Fas was markedly up-regulated in LS174T cells treated with MPA,and more importantly, combined with chemotherapy drugs , the effect of inhibition was more significant than single agent.The direct via gastrointestinal gavage of MPA could suppress colonic cancer growth in nude mice with the tumor growth inhibitory rate being 54.2%. Growth was found to arrest in G₁ phase.The apoptotic rate and cell surface Fas expression in cancer cells increased after treated with MPA.Fas/FasL expression in the treated tumor tissue ascended noticeably as compared with the controls.Conclusion: MPA had significant inhibition effect on the growth of LS174T human colon cancer cells.It results from causing growth arrest in G₁ phase , MPA could induce apoptosis of LS174T cells. The mechanism may relate to Fas/FasL upregulation on the surface of cancer cells .