Effect Of Low Dose Fractionated Radiation On Reversing Cisplatin Resistance In Ovarian Carcinoma Via VEGF And MTOR

Objective:To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF)and mammalian target of rapamycin(mTOR)in vivo.Methods : Human cisplatin-resistance ovarian carcinoma cells(SKOV3/DDP)were injected in nude mice to establish ovarian cancer xenografts.The mice were randomly divided into three groups: a control group,a low dose fractionated radiation(LDRFT)and a conventional dose radiation group.Each group was exposed to 0c Gy,50 c Gy and200 c Gy radiation respectively for 4 weeks,totally 8.0Gy.Mice in LDFRT group were radiated twice daily for 2 days,with 6 hours intermission on day1,2 of every week,totally 4 weeks.Conventional dose group mice were given 200 c Gy single radiation one day on day 1 per week,totally 4 weeks.Maximum horizontal and vertical diameters of the tumor were measured every other day for drawing the tumor growth curve.After 4weeks of irradiation,we dissected the tumor tissue and calculated the tumor inhibition rate.RT-PCR detected the expression of VEGF?mTOR,and Western Blotting detected the expression of corresponding proteins.Results Both LDRFT and conventional dose radiation could inhibit the growth of tumor cells,and compared with the control group were significantly different(P<0.05).The rate of tumor inhibition in LDFRT group(37.5603%)was lower than that in conventional dose group(47.4446%),but there was no significant difference(P?0.05).Compared with the other two groups,the m RNA expression of VEGF was significantly lower in LDFRT group(P<0.05).But there was no obvious difference between conventional-dose and control group.No obvious difference among the three groups about the m RNA expression of mTOR,but the protein of p-mTOR was lower in LDFRT group(P<0.05).The Western Blotting experiment confirmed the conclusions by the expression of proteins level.Conclusion LDFRT could inhibit the growth of tumor cells as well as conventional dose irradiation.In addition,LDFRT could deregulate the expression of VEGF and p-mTOR,which may plays a vital role in reversing cisplatin-resistance in ovarian cancer.