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| Arsenic trioxide achieves radiosensitization by inhibiting DNA damage repair |
| GAO Xingxing1,2, HUI Hui1,2, REN Hongrong1,2, ZHOU Yun1,2 |
1. Department of Affiliated The First Clinical Medical College of Xuzhou Medical University, Xuzhou 221000 China;
2. Xuzhou Central Hospital, Xuzhou 221000 China |
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Abstract Objective To explore the radiosensitizing effect of arsenic trioxide (ATO) in cervical cancer, and to further explore the underlying mechanism related to DNA damage repair. Methods Human cervical cancer cells (Siha and Hela cells) were cultured in vitro, treated with different concentrations of ATO, and the cell proliferation was detected by CCK-8 assay. The cells were divided into four groups: control group, radiotherapy (IR) group, ATO group, and radiotherapy + ATO (IR + ATO) group. Radiosensitization ratio was determined by plate cloning assay, cell cycle and apoptosis by flow cytometry, the expression of γH2AX by immunofluorescence, the expression of Cyclin B1, PTEN, and RAD51 by Western blot, and the expression of RAD51 mRNA by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results CCK-8 showed that ATO at concentrations of 1 μM and higher could significantly inhibit the proliferation of Siha and HeLa cells. Plate cloning showed that ATO had a radiosensitizing effect on cervical cancer, and the radiosensitization ratios were 1.37 and 1.30, respectively. Flow cytometry showed that the proportion of cell cycle arrest was significantly higher in the IR + ATO group than that in the control group (P < 0.001). The apoptosis rate was significantly higher in the IR + ATO group than that in the control group (P < 0.01). Western blotting showed that the expression levels of PTEN and RAD51 proteins significantly decreased (P < 0.05) and the expression level of Cyclin B1 protein significantly increased (P < 0.05) in the IR + ATO group. Conclusion ATO achieves radiosensitization in cervical cancer through blocking the DNA homologous recombination repair pathway by consuming PTEN.
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Received: 26 January 2024
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