Study On Effect Of Imatinib Mesylate On The Growth And Apoptosis Of Cisplatin-resistant Human Ovarian Cancer Cell Line SKOV3/DDP

Objective To investigate the targeted therapy drug imatinib mesylate inhibitory effecton the proliferation and apoptosis of the cisplatin resistant human ovarian cancer cellline SKOV3/DDP，to explore its effect on drug sensitivity of SKOV3/DDP to cisplatin.Methods1Cisplatin in the different dose concentratios (5.0～160.0mg/L) and imatinib mesylate in the differrent dose concentrations (1.0～20.0μumol/L)were added into the ovarian carcinoma cisplatin resistant cell line SKOV3/DDP alone orin combination. MTT assay were used for the detection of the proliferation inhibition ofSKOV3/DDP cells. IC50was calculated according to the inhabitationrated. RI(reverse, index,) and RF (reverse fold) of d imatinib mesylate was calculatedaccording to IC50.2Flow cytometry was used to detect the effcct on the cell cycle andapoptosis rate of the SKOV3/DDP cell48h later following imatinib mesylate andCisplatin (5.0mg/L) monotherapy and combination therapy.Results1Both SKOV3cells and SKOV3/DDP cells were adherent cells, they grewslowly after imatinib was added. At the same time, the cell shrinked to round or oval.There was large particles and bright spot appeared in the cytoplasm as well asgaps between cells. At last the cell detached from the wall and debris was visible. Withthe increase of concentration of imatinib and time the change became more obvious.2Different concentrations of imatinib mesylate have a certain inhibitory effecton SKOV3/DDP cells, and the effcet shows a time and dose dependent.3Differentconcentrations of imatinib mesylate and Cisplatin had effect on SKOV3/DDP48h, therewas difference in cells growth inhibition ratebetween the combination group and imatinbmesylate monotherapy group significantly (P<0.05), Imatinib mesylate shew synergisticeffect with Cisplatin and imatinib mesylate in5μmol/L shew the most synergisticeffect.4Imatinib mesylate at5μmol/L combined with Cisplatin on SKOV3/DDP cellsfor48h, we saw imatinib mesylate significantly enhanced the drug sensitivity ofSKOV3/DDP cells to cisplatin (P<0.05).5When Imatinib mesylate in1.0,2.5,5.0μmol/Lwas combined with Cisplatin, resistance index of SKOV3/DDP cells were:27.60±0.75,19.61±0.63,12.24±0.24while imatinib mesylate reverse cells resistant to Cisplatin by1.44,2.03,3.25times.6Flow cytometry showed that imatinib mesylatecaused G1/G2phase arrest. Arrest of S phase was more obvious when imatinib mesylateadded into Cisplatin. the percentage of S phase increased significantly in combinationgroup compared with Cisplatin added singlely.7Apoptosis detected by flow cytometryshew that imatinib mesylate induced cell apoptosis with increasing of concentration.When the concentration of Cisplatin is low, apoptosis inducd by it is weak, but whencombined with imatinib mesylate, the apoptosis rate was significiently higher than thosein the monotherapy group. Imatinib mesylate inducd apoptosis of drug-resistant cells aswell as enhanced the ability of Cisplatin.Conclusion1Imatinib mesylate have a certain inhibitory effect on SKOV3/DDP with atime and dose dependent.2Imatinib mesylate increased the sensitivity of SKOV3/DDPon cisplatin and reversed its drug resistance.3Imatinib mesylate caused G0/G1phasearrest as well as the percentage of S phase caused by cisplatin.4Imatinib mesylateinduced apoptosis of SKOV3/DDP cells as well as enhanced the ability of Cisplatin.