| 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. |
| 低剂量分次照射通过VEGF、mTOR逆转卵巢癌顺铂耐药机制的体内研究 |
| 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 |
| DOI：10.1007/s10330-017-0229-9 |
| 中文关键词: 低剂量分次照射；卵巢癌；逆转；SKOV3/DDP；血管内皮生长因子；哺乳动物雷帕霉素靶蛋白 |
| 英文关键词: low-dose fractionated radiation; ovarian carcinoma; resistance; SKOV3/DDP; VEGF; mTOR |
| 基金项目: |
| 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 | |
|
| Hits: 9989 |
| Download times: 11302 |
| 中文摘要: |
| 目的：以卵巢癌荷瘤裸鼠为模型，探究低剂量分次照射通过VEGF、mTOR逆转卵巢癌顺铂耐药的机制。
方法：将耐顺铂卵巢癌细胞（SKOV3/DDP）接种于裸鼠，建立卵巢癌裸鼠模型。将其随机分为三组：对照组，低剂量照射组，常规剂量照射组。对照组不给予照射。低剂量组每周的第1、2天给予照射，每天2次，每次0.5Gy，间隔6小时；共照射4周，总剂量8Gy。常规剂量组仅每周的第1天给予1次照射，2Gy，共照射4周，总剂量8Gy。隔天测量肿瘤的最大长径和垂直径，绘制肿瘤生长曲线；4周照射完毕后，剥离肿瘤组织，计算抑瘤率。RT-PCR从基因水平检测VEGF、mTOR和p-mTOR的相对表达量，Westernblot检测相应蛋白的表达量。
结果：通过绘制肿瘤曲线可知：低剂量分次照射和常规剂量照射均可抑制肿瘤细胞生长，与对照组相比有明显差异（P<0.05），差异具有统计学意义；低剂量照射组抑瘤率（37.5603%）低于常规剂量照射组抑瘤率（47.4446%），二者之间差异无统计学意义（P＞0.05）。与对照组和常规剂量照射组相比，低剂量照射组VEGF、p-mTOR的 mRNA表达明显降低（P<0.05）差异具有统计学意义，而常规剂量照射组与对照组之间无明显差异；mTOR的表达在三个组中无明显差异；Western Blot从蛋白表达水平印证了以上结论。
结论：低剂量分次照射可抑制肿瘤生长。
低剂量分次照射可通过调节VEGF、mTOR的表达逆转卵巢癌顺铂化疗耐药。 |
| 英文摘要: |
| 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. |
|
View Full Text
Download reader HTML全文 |
| Close |