Curcumin Exerts Anti-tumor Effects On Diffuse Large B Cell Lymphoma Via Regulating PPAR?/Akt Pathway

BackgroundLymphoma originate from lymph nodes and lymphoid tissues,is a kind of hematological malignancies.Base on the histopathological changes,lymphoma can be divided into Hodgkin's lymphoma(HL)and non-Hodgkin's lymphoma(NHL),NHL accounts for about 90% of all lymphoma,and consists of B cell type and T / NK cell type.Diffuse large B-cell lymphoma(DLBCL)is the most common NHL subtype,accounting for about 35%-40%,and their molecular types and clinical manifestations are highly heterogeneous.With the introduction of Rituximab,R-CHOP has become the first-line chemotherapy regimen,which obviously improved the overall response rate and survival of DLBCL patients,but still about 30% of patients showed resistance during the treatment or early relapse after completing 6-8 cycles chemotherapy,and the prognosis of these patients is extremely poor.Therefore,it is of great clinical significance to find more effective treatment targets and new treatment schemes,or to improve the efficiency of existing treatment schemes.Curcumin is a plant polyphenol extracted from curcuma longa,which has become a research hotspot and attracted increasing attention due to its multiple pharmacological effects with little toxicity and side effects.Anti-cancer remains one of its main effects,it has been found that curcumin can play a tumor suppressive role in diverse malignant tumors,such as colon cancer,breast cancer,lung cancer,liver cancer,cervical cancer and relevant clinical trials have been in progress,but whether curcumin owns anti-lymphoma effect on DLBCL and the further mechanism remains unclear.ObjectiveTo investigate the possibility of curcumin in the treatment of human diffuse large B cell lymphoma,and to elucidate the mechanism of curcumin in inhibiting DLBCL proliferation,promoting apoptosis and blocking the cell cycle.Methods1.Human diffuse large B cell lymphoma cells Ly1 and Ly3 were cultured in vitro.Cell viability was measured by CCK-8 after treatment with different concentrations of curcumin.2.Apoptosis and cell cycle were detected by flow cytometry after treated with 5 ?mol/L or 10?mol/L curcumin for 24 h.3.The expression of PPAR? and Akt signaling pathway-related proteins Akt,p-Akt,mTOR,p-mTOR and apoptosis-related proteins Cleaved Caspase3 were detected by western blot after treated with 10 ?mol/L curcumin for different time(0,2,4,8,12 h).4.The expression of PPAR? and Akt signaling pathway-related proteins Akt,p-Akt,mTOR,p-mTOR and apoptosis-related proteins Cleaved Caspase3 were detected by western blot after PPAR? antagonist GW9662(10 ?mol/L)or agonist Rosiglitazone(20?mol/L)treated for 24 h.5.Ly1 cells were treated with 10?mol/L curcumin along with PPAR? antagonist GW9662(10 ?mol/L)or agonist Rosiglitazone(20?mol/L)and repeated above experiments.6.Ly1 cells were injected into NOD / SCID mice subcutaneously to establish a lymphoma model,then mice were injected with curcumin to observe the condition of mice and the size of the transplanted tumors,tumors were dissected and immunohistochemical staining of PPAR? was performed at the end.Results1.The results of CCK-8 showed that during the concentration range of 0-40?mol/L,curcumin inhibited the proliferation of diffuse large B cell lymphoma in a concentration-dependent manner.2.Flow cytometry results showed that 5 ?mol/L and 10?mol/L curcumin promoted apoptosis and arrested cells in G2 phase,besides,10?mol/L curcumin showed a more significant inhibition(P<0.05).3.Western blot results showed increased PPAR? and cleaved caspase3 protein levels,while decreased p-Akt and p-mTOR protein levels with time after 10?mol/L curcumin treated,which was the same as rosiglitazone treated but opposite with GW9662 treated.4.The effects of curcumin were partially abrogated by PPAR? antagonist GW9662 but enhanced by the agonist Rosiglitazone.5.The transplanted lymphoma model was successfully constructed,and curcumin can inhibit the growth of transplanted lymphoma,the expression of PPAR? in the curcumin injection group was higher.Conclusion1.Curcumin inhibits the proliferation,promotes the apoptosis of diffuse large B cell lymphoma and arrested cells at G2 phase.2.The effects of curcumin on DLBCL achieved by up-regulating the expression of PPAR? and further inhibiting the Akt signaling pathway.