| Xingyan JU,Shihai liu,Hongsheng Yu,Donghai Liang,Tao Jiang,Ronghui Yuan,Wei Zhao. Effect of low dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via VEGF and mTOR*. Oncol Transl Med, 2017, 3: 143-150. |
| Effect of low dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via VEGF and mTOR* |
| Received:May 13, 2017 Revised:August 10, 2017 |
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| KeyWord:low-dose fractionated radiation; ovarian carcinoma; resistance; SKOV3/DDP; VEGF; mTOR |
| Author Name | Affiliation | E-mail | | Xingyan JU | the Affiliated Hospital of Qingdao University | xyjuqd@126.com | | Shihai liu | the Affiliated Hospital of Qingdao University | | | Hongsheng Yu | the Affiliated Hospital of Qingdao University | qdhsyu@126.com | | Donghai Liang | the Affiliated Hospital of Qingdao University | | | Tao Jiang | the Affiliated Hospital of Qingdao University | | | Ronghui Yuan | the Affiliated Hospital of Qingdao University | | | Wei Zhao | the Affiliated Hospital of Qingdao University | |
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| 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. |
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