Low-glucose combined with palmitic acid enhances the radiosensitivity of colorectal cancer through inducing reactive oxygen species generation and DNA damage
10.3760/cma.j.cn113030-20210119-00025
- VernacularTitle:低糖联合棕榈酸通过诱导活性氧产生和DNA损伤促进结直肠癌细胞放射增敏
- Author:
Hao KUANG
1
;
Jinlin KANG
;
Fen WANG
;
Fuxiang ZHOU
Author Information
1. 武汉大学中南医院肿瘤放化疗科/湖北省肿瘤医学临床研究中心/肿瘤生物学行为湖北省重点实验室 430071
- Keywords:
Low-glucose combined with palmitic acid;
Metabolic stress;
Reactive oxygen species;
Radiosensitization
- From:
Chinese Journal of Radiation Oncology
2021;30(6):619-624
- CountryChina
- Language:Chinese
-
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 potential and apoptosis rate were detected by flow cytometry. The changes in the radiosensitivity were detected by immunofluorescence-based γ-H 2AX 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-H 2AX foci was significantly increased ( P<0.05), and the D 0 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-H 2AX 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-H 2AX 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.
