| Xiangmin Jia,Shihai Liu,Jie Ming,Xiaofei Nie,Donghai Liang,Tao Jiang,HongshengYu. Low-dose fractionated radiation reverses cisplatin resistance in ovarian cancer cells via PI3K/AKT/GSK-3β signaling. Oncol Transl Med, 2017, 3: 203-209. |
| 低剂量分次照射通过PI3K/AKT/GSK-3β信号通路逆转卵巢癌顺铂耐药的作用及机制研究 |
| Low-dose fractionated radiation reverses cisplatin resistance in ovarian cancer cells via PI3K/AKT/GSK-3β signaling |
| Received:December 08, 2016 Revised:October 16, 2017 |
| DOI：10.1007/s10330-016-0213-3 |
| 中文关键词: 低剂量分次照射；顺铂耐药；卵巢癌；PI3K/AKT/GSK-3β信号通路 |
| 英文关键词: low-dose fractionated radiation (LDFRT); cisplatin-resistance; ovarian cancer; PI3K/AKT/GSK-3β pathway |
| 基金项目: |
| Author Name | Affiliation | E-mail | | Xiangmin Jia | Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China | 386303816@qq.com | | Shihai Liu | Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China | | | Jie Ming | Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China | | | Xiaofei Nie | Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China | | | Donghai Liang | Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China | | | Tao Jiang | Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China | | | HongshengYu* | Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China | qdhsyu@126.com |
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| 中文摘要: |
| 目的：研究PI3K/AKT/GSK-3β信号通路在卵巢癌顺铂耐药机制中的作用以及低剂量分次照射通过PI3K/AKT/GSK-3β信号通路逆转卵巢癌顺铂耐药的作用及机制。
方法：将卵巢癌癌耐顺铂细胞SKOV3/DDP细胞分为3组：低剂量分次照射组、常规剂量照射组以及对照组。每组中细胞分别都用不同浓度的顺铂（0, 1.25, 2.5, 5, 10, 20μg/ml）处理48小时。CCK8测定三个组中细胞的增殖抑制率；流式细胞术测定细胞的凋亡率；Western blot测定AKT, P-AKT, GSK-3β, P- GSK-3β, P21, CyclinD1 和 P27 蛋白的水平。
结果：低剂量分次照射组细胞的增殖抑制率和凋亡率明显高于常规剂量照射组和对照组；低剂量分次照射组中P-AKT, P-GSK-3β 和 CyclinD1 表达水平明显升高, P21 和 P27表达明显降低，而AKT和GSK-3β表达水平无明显变化。
结论：PI3K/AKT/GSK-3β信号通路在卵巢癌顺铂耐药机制中发挥着重要的作用；低剂量分次照射通过抑制PI3K/AKT/GSK-3β信号通路的活性逆转卵巢癌顺铂耐药。 |
| 英文摘要: |
| Objective To investigate whether low-dose fractionated radiation (LDFRT) could enhance cisplatin
sensitivity in drug-resistant human ovarian cancer cells SKOV3/DDP, and to further explore the underlying
mechanism.
Methods SKOV3/DDP ovarian cancer cells were divided into three groups as follows: control, LDFRT, and
conventional-dose radiation groups. Cells from all three groups were treated with different concentrations
of cisplatin (0, 1.25, 2.5, 5, 10, and 20 μg/mL) for 48 h. The proliferation inhibition rate was investigated
using the cell counting kit 8 (CCK8). The rate of apoptosis was determined by flow cytometry (FCM). Protein
levels of AKT, P-AKT, GSK-3β, P-GSK-3β, P21, cyclin D1, and P27 were examined by Western blotting.
Results As expected, LDFRT significantly reduced the half-maximal inhibitory concentration (IC50) of
cisplatin and promoted apoptosis in SKOV3/DDP cells. Moreover, in the LDFRT group, protein levels of
P-AKT, P-GSK-3β, and cyclin D1 were markedly decreased, those of P21 and P27 were greatly increased,
and total AKT and GSK-3β levels showed no significant difference compared to those in both the control
and conventional-dose radiation groups.
Conclusion LDFRT sensitizes resistant SKOV3/DDP ovarian cancer cells to cisplatin through inactivation
of PI3K/AKT/GSK-3β signaling. |
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