Experiment Study Of Augmenting Chemosensitivity Of Multiple Myeloma Cell To Chemotherapeutic Drug Via Parthenolide

PartⅠParthenolide enhance the antimyeloma effect of Dexamethasone and AdriamycinObject: To study the combined anti-tumor effect of PTL with Dexamethasone or Adriamycin on MM cell.Method: Human myeloma cell line RPMI8226 was treated with PTL (0,0.5,1,2μmol/L)combined with ADM(0,0.01563,0.03125,0.0625,0.0125,0.25,0.5,1,2,4,8μmol/L)or Dex(0,0.001,0.005,0.025,0.125,0.625μmol/L),after different times(48h,72h),the cell proliferation was detected by MTT assay, cell apoptosis was detected by Annexin-V/PI with flow cytometry and AO/EB staining.Result:(1)The IC50 of ADM to RPMI8226 was 0.55±0.06μmol/L ,but when combined with PTL 0.5,1,2μmol/L,it reduced to 0.51±0.04μmol/L,0.28±0.03μmol/L(p<0.05),0.25±0.02μmol/L (p<0.05),respectively;after 72h treated,compared with the control group,cell proliferation rate of 0.005μmol/L Dex group was 54±0.9%,the combined group(with 1umol/L PTL)reduced to 36±1%(p<0.01).(2)We observed typical apoptosis changes at morphology approach. Apoptosis rates,checked by Annexin-V/PI,were 50±7% (p<0.05) in the combined group,higher than PTL(2μmol/L)group,15±3% and ADM(0.25μmol/L)group ,20±2.5%.Conclusion:PTL can enhance the anti-myeloma effect of ADM and Dex,which mainly inducing cell apoptosis. PartⅡThe mechanism of chemosesitization by PTL in MM cellObject: MM is still an incurable disease. Chemotherapy is often used, but has serious side effects, and may develop to drug resist. We found that PTL may help to overcome these problems. So we investigate the mechanism of chemosensitization via PTL in RPMI8226 cells in this part. And want to show some envidence for the future study of chemosensitization in MM.Method: After RPMI8226 cell was treated with various concentrations of ADM and PTL,NFκB was measured by EMSA,6h later; the mRNA content of gene Bcl-2,Fas,Survivin were determined by RT-PCR 48h later.Result: PTL could suppressed the NFκB at a dose dependent manner, 1μmol/L (and above) PTL strongly suppressed the NFκB in RPMI8226 cell after treated 6 h.ADM could activate the NFκB in MM cell. Compared with the control group(ADM 0μmol/L),ADM 2μmol/L doubled the level of NFκB. And PTL (1μmol/L) could also suppress the NFκB enhancing effect of ADM. After treated with 0.5～8μmol/L PTL 48 h,the mRNA contents of Bcl-2,Survivin decreased at a concentration dependent manner, but with no influence on Fas.Conclusion:PTL can suppress MM cell and drug induced NFκB activation, induce apoptosis and act as a chemosensitizer.