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 NameAffiliationE-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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