ObjectiveTo 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.MethodsSKOV3/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.ResultsAs 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.ConclusionLDFRT sensitizes resistant SKOV3/DDP ovarian cancer cells to cisplatin through inactivation of PI3K/AKT/GSK-3β signaling.
ObjectiveTo investigate the inhibition of low dose radiation (LDR) on S180 sarcomas and its modulation of MMP-2 and TIMP-2 in mice.MethodsS180 subcutaneously implanted tumor model mice were randomly divided into two groups: control (N) and low dose radiation (LDR) groups. N mice were sacrificed after 12 h, whereas LDR mice were sacrificed after 12 (LDR-12 h), 24 (LDR-24 h), 48 (LDR-48 h), and 72 (LDR-72 h) h. Thereafter, we measured the tumor volumes. Histopathology was performed, and P-V immunohistochemistry was applied to assess MMP-2 and TIMP-2 expression.ResultsCompared with the control group, the tumor growth was significantly inhibited in the LDR groups (P < 0.05). MMP-2 expression was considerably reduced in LDR-24h (P < 0.05) and LDR-48h (P < 0.05), whereas the change of TIMP-2 was not obvious in the LDR groups (P > 0.05) in contrast to that of the control group.ConclusionLDR can effectively suppress the growth of S180 implanted tumors by reducing MMP-2, which is associated with invasion and metastasis.
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