Affiliation:
1. Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
2. Department of Ultrasound, The Central Hospital of Linyi, Linyi 276400, China
Abstract
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)