Effect of low dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via VEGF and mTOR ⁎

Abstract

Abstract 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-resistant ovarian carcinoma cells (SKOV3/DDP) were injected into nude mice to establish ovarian cancer xenografts. The mice were randomly divided into three groups: a control group, a low-dose fractionated radiation (LDRFT) group, and a conventional-dose radiation group. Each group was exposed to 0 cGy, 50 cGy, and 200 cGy radiation, respectively, for 4 weeks, up to a total of 8.0 Gy. Mice in the LDFRT group were irradiated twice daily with 6 hour intermissions on day 1 and 2 of every week for a total of 4 weeks. Conventional-dose group mice were given a single 200 cGy radiation dose on the first day each week for a total of 4 weeks. Maximum horizontal and vertical diameters of the tumors were measured every other day and used to create a tumor growth curve. After 4 weeks of irradiation, we dissected the tumor tissue and calculated the tumor inhibition rate. RT-PCR detected the expression of VEGF and mTOR, and Western blots detected the expression of corresponding proteins. Results Both LDRFT and conventional-dose radiation inhibited the growth of tumor cells, and growth of tumors in the two radiation groups compared with growth in the control group were significantly different (P < 0.05). The rate of tumor inhibition in the LDFRT group (37.5603%) was lower than in the conventionaldose group (47.4446%), but there was no significant difference (P > 0.05). Compared with the other two groups, the mRNA expression of VEGF was significantly lower in the LDFRT group (P < 0.05), but there was no obvious difference between the conventional-dose and control groups. There was no obvious difference in the mRNA expression of mTOR among the three groups, but the expression of the protein p-mTOR was lower in the LDFRT group (P < 0.05), as confirmed by Western blotting. Conclusion LDFRT is as effective at inhibiting the growth of tumor cells as conventional-dose radiation. In addition, LDFRT could deregulate the expression of VEGF and p-mTOR, and may therefore play a vital role in reversing cisplatin resistance in ovarian cancer.