水杨酸通过激活AMPK/TSC2/mTOR通路使宫颈癌细胞对放疗增敏

Q1 Health Professions Radiation Medicine and Protection Pub Date : 2022-03-01 DOI:10.1016/j.radmp.2022.01.005

Shun Lu , Wenjing Ye , Jie Zhou , Guangming Yi , Jianming Huang , Siyao Deng , Minglun Li , Yimin Li , Yanqiong Song , Jiayu Zhang , Lichun Wei , Guiquan Zhu , Jinyi Lang

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引用次数: 0

摘要

目的探讨水杨酸(SA)对人宫颈癌细胞的放射增敏作用及其可能的分子机制。方法分别用SA和电离辐射处理宫颈癌细胞。免疫荧光法检测γ-H2AX的表达。流式细胞术分析细胞周期和凋亡情况。Western blot检测AMPK/TSC2/mTOR通路蛋白表达水平。结果sa对宫颈癌细胞基底增殖的抑制作用呈剂量依赖性和时间依赖性。此外，SA增加了辐射诱导的DNA损伤，促进了细胞凋亡，引发宫颈癌细胞周期由G2-M期向G1-S期重新分布，从而增加了细胞对辐射的敏感性。此外，SA处理提高了P - ampk α的表达水平(t = 3.996, P <0.05)和P - tsc2 (t = 5.308, P <0.05),而p-mTOR水平(t = 10.160, P & lt;0.05)显著降低。结论sa通过靶向AMPK/TSC2/mTOR信号通路增强宫颈癌细胞的放射敏感性，可能是提高宫颈癌放疗疗效的一种有前景的治疗策略。

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Salicylic acid sensitizes cervical cancer cells to radiotherapy by activating AMPK/TSC2/mTOR pathway

Objective

To investigate the radio-sensitizing effect of salicylic acid (SA) on human cervical cancer cells and its potential molecular mechanism.

Methods

Cervical cancer cells were treated with SA and ionizing radiation. The expression of γ-H2AX was evaluated by immunofluorescence (IF) assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to detect the protein level of AMPK/TSC2/mTOR pathway.

Results

SA inhibited basal proliferation of cervical cancer cells in a dose and time dependent manner. In addition, SA increased radiation-induced DNA damage, promoted apoptosis, triggered a redistribution of cell cycle from G₂-M phase to G₁-S phase of cervical cancer cells, and hence increased cell sensitivity to radiation. Moreover, SA treatment elevated the expression levels of p-AMPKα(t = 3.996, P < 0.05) and p-TSC2(t = 5.308, P < 0.05), whereas the level of p-mTOR (t = 10.160, P < 0.05) was significantly decreased.

Conclusion

SA enhances the radiosensitivity of cervical cancer cells by targeting AMPK/TSC2/mTOR signaling pathway, and might serve as a promising therapeutic strategy to improve the efficacy of radiotherapy for cervical cancer.

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