The Study Of DHA Enhanced Chemotherapy Sensitivity Of Human Ovarian Cancer SKOV3/DDP Cells In Nude Mice

Objective:To investigate whether dihydroartmisinin can improve the sensitivity of human ovarian cancer cell line SKOV3/DDP to chemotherapeutic drugs,and what effect of expression of anti apoptosis protein XIAP in ovarian cancer cells,and to further explore the related mechanism.Methods:Cultivate human ovarian cancer cell line SKOV3/DDP of chemotherapy resistance in vitro, and make the cell suspension 6 * 106 /(0.2ml/) before cultured to logarithmic phase,inoculated in lack of cell immunity of BALB/c nude mice under the armpit, the nude mice subcutaneous tumor diameter up to 500mm3-1000mm3 when modeling successful, 20 nude mice were divided into 4 groups(each of which was composed of six nude mice):Cisplatin control group(final concentration: 2mg/kg), blank control group(edible oil), low dose of dihydroartemisinin(final concentration: 100mg/kg) + cisplatin group, high dose of dihydroartemisinin(final concentration: 200mg/kg) + cisplatin group, blank control group and dihydroarteannuin group gavage every day timely,cisplatin group intraperitoneal injection every two days, and record the weight curve of nude mice, nude mice were sacrificed 10 days, weighing tumor weight, calculate the inhibition rate of tumor in nude mice,detected the expression of XIAP mRNA in chemotherapy resistance human ovarian cancer xenografts by RT-PCR, immunohistochemical staining used to detect the XIAP protein expression.Results:1. Pathological detection: the majority of parenchymal cells is in tissue, large volume,and permutation disorder, the karyoplasmic proportion increased, tumor cells in DHA combined cisplatin group has found different degrees of nucleus fcondensation,ragmentation and apoptotic, and fibrous hyperplasia.2.DHA obviously inhibite growth of transplanted tumors of SKOV3/DDP cells,and depending on drug concentration, low and high dose of DHA groups measured tumor inhibition rate of28.42% and 51.91%, compared with cisplatin and blank groups, the difference was statistically significant, P < 0.05.3.Used RT-PCR and SP method to confirm that blank group compare with cisplatin group was no statistically significant, P > 0.05, XIAP gene and protein expression were higher in DHA combined with cisplatin group than other, P <0.05, and have Inverse relation with DHA concentration.Conclusion:Dihydroartemisinin can reverse multidrug resistanceon on subcutaneous transplantation tumor in nude mice;in the group of dihydroartemisinin combine with cisplatin,the rate of tumor inhibition were significantly higher than the control group and cisplatin group, suggesting that dihydroartemisinin can improve the sensitivity of tumor cells to cisplatin; the expression of XIAP in dihydroartemisinin combine with cisplatin group compared with the control group and DDP group significantly reduced,confirmed dihydroartemisinin by promoting SKOV3/DDP cells apoptosis in reversing resistance to chemotherapy, and the mechanism of apoptosis related.