Low-glucose combined with palmitic acid enhances the radiosensitivity of colorectal cancer through inducing reactive oxygen species generation and DNA damage
Kuang Hao, Kang Jinlin, Wang Fen, Zhou Fuxiang
Department of Radiation & Medical Oncology, Zhongnan Hospital of Wuhan University, Clinical Cancer Study Center, Key Laboratory of Tumor Biological Behavior of Hubei Provence, Wuhan 430071, China
Abstract：Objective To investigate the mechanism underlying the inhibiting effect of low-glucose combined with palmitic acid on human colon cancer cells and its influence on the radiosensitivity. Methods Under the treatment of low-glucose, palmitic acid and low-glucose combined with palmitic acid, the treatment condition that significantly inhibited the proliferation of SW480 was screened by CCK-8 assay. The reactive oxygen species (ROS) level, mitochondrial membrane potentialand apoptosis rate were detected by flow cytometry. The changes in the radiosensitivity were detected by immunofluorescence-based γ-H2AX quantification and colony formation assay. The protein expression level was detected by Western blot. Results Compared with the control group, the condition of low-glucose combined with 120μmol/L palmitic acid significantly inhibited the proliferation of SW480 cells (P<0.01). The expression levels of CPT1a, PFKFB3 and PKM were significantly up-regulated, the expression levels of NDUFV1, NDUFV2 and NDUFS1 were remarkably down-regulated, the ROS level was significantly increased and the ATP level was considerably reduced in the cells under metabolic stress (all P<0.01). After irradiation, the number of γ-H2AX foci was significantly increased (P<0.05), and the D0 value was significantly reduced (P<0.01),the ROS level was considerably increased (P<0.001), the apoptosis rate was significantly increased (P<0.001) and the expression level of γ-H2AX protein was remarkably up-regulated (P<0.01) in the low-glucose combined with 120μmol/L palmitic acid group. Pretreatment with NAC could reverse the changes of ROS, apoptosis and γ-H2AX protein expression. Conclusions The combination of low-glucose and palmitic acid can induce metabolic stress in SW480 cells, inhibit tumor proliferation and increase the radiosensitization when combined with radiotherapy by inducing the generation of ROS and DNA damage.
Kuang Hao,Kang Jinlin,Wang Fen et al. Low-glucose combined with palmitic acid enhances the radiosensitivity of colorectal cancer through inducing reactive oxygen species generation and DNA damage[J]. Chinese Journal of Radiation Oncology, 2021, 30(6): 619-624.
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2021, Vol. 30 
