The Role And Mechanism Of Inhibiting The Key Fatty Acid Synthesis Enzymes In Burkitt’s Lymphoma

Objective Burkitt’s lymphoma(BL),a highly aggressive B-cell Non-Hodgkin’s lymphoma,is the most rapidly occurring tumor in humans,althoμgh it is highly sensitive to chemotherapy,its high treatment costs make it less effective.Lipid metabolism was significantly enhanced in Burkitt’s lymphoma.Fatty acid synthase(FASN)and Stearoyl-CoA desaturase 1(SCD1)are speed-limiting enzymes in the process of DE novo fatty acid synthesis.Therefore,targeting FASN and SCD1 can provides a new clinical approach for the treatment of Burkitt’s lymphoma.We hypothesized that PPT could effectively kill Burkitt’s lymphoma by disrupting with the lipid metabolism.Methods 1.SCD1 and FASN expressions of Burkitt’s lymphoma were detected by Bioinformatics analysis、Western blotting and RT-PCR.2.CCK8,Western blotting and flow cytometry were used to detect the expression of SCD1 and FASN in Raji and CA46 cell lines and the changes of cell proliferation and apoptosis after PPT.3.CCK8 and flow cytometry were used to detect the changes of cell proliferation and apoptosis of Raji and CA46 cell lines after the action of PPT and the addition of exogenous oleic acid or palmitic acid.4.In vivo experiments,HE staining and immunohistochemistry were used to further verify the efficiency and safety of PPT in killing Burkitt’s lymphoma.Results 1.The key fatty acid synthesis enzymes SCD1 and FASN are highly expressed in Burkitt’s lymphoma.2.PPT downing the expression of SCD1 and FASN in Burkitt’s lymphoma cell lines,and concentration-dependent inhibited the proliferation of Burkitt’s lymphoma cells and induced cell apoptosis.3.The addition of exogenous oleic acid could reverse the killing effect of PPT on Burkitt’s lymphoma cell lines,while the addition of exogenous palmitic acid could not.4.In vivo experiments showed that PPT could inhibit tumor volume growth and the expression of SCD1 and FASN.Conclusions In vivo and in vitro experiments confirmed that(20S)-protopanaxatriol could kill Burkitt’s lymphoma in a concentration dependent manner and play an anticancer role by inhibiting the overexpressed key fatty acid synthesis enzymes SCD1 and FASN.The addition of exogenous oleic acid could reverse the killing effect of PPT.