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. |
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 |
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KeyWord:low-dose fractionated radiation (LDFRT); cisplatin-resistance; ovarian cancer; PI3K/AKT/GSK-3β pathway |
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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Abstract: |
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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