4-羟基水杨酰苯胺可影响T淋巴细胞白血病肿瘤增殖与凋亡
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1.安徽医科大学上海临床学院;2.上海市东方医院

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国家自然科学基金,国家自然科学基金项目(面上项目,重点项目,重大项目)


4-hydroxysalicylaniline can affect the proliferation and apoptosis of T lymphoblastic leukemia
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Shanghai Clinical College, Anhui Medical University

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    摘要:

    目的:研究4-羟基水杨酰苯胺(RC17)对T淋巴细胞白血病细胞Jurkat和Hut-78增殖与凋亡的影响。方法:梯度浓度的RC17处理Jurkat和Hut-78细胞后,以CCK8和琼脂克隆形成实验,检测细胞增殖状况;用细胞流式术检测细胞周期和凋亡水平;以γ-H2AX免疫荧光染色检测DNA损伤状况;通过Western blot检测周期、凋亡和DNA损伤相关蛋白的表达水平。皮下注射Jurkat细胞构建小鼠肿瘤模型,注射RC17,记录小鼠体重与肿瘤体积变化,13天后,取肿瘤组织,通过HE染色观察组织形态,并通过Ki67和γ-H2AX的免疫组织化学染色,分析药物对肿瘤组织增殖与DNA损伤的影响。结果:在体内和体外,证明了RC17可通过诱导Jurkat和Hut-78细胞 S 期细胞周期阻滞与凋亡,并且通过CHK1/CHK2信号通路的磷酸化激活,加重DNA损伤,抑制T淋巴细胞白血病肿瘤,但RC17对小鼠无明显毒性。结论: 综上所述,RC17可作为潜在的抗T淋巴细胞白血病药物;RC17这一效应是通过CHK1/CHK2信号通路影响DNA损伤修复过程而完成。

    Abstract:

    Objective: To investigate the effect of 4-hydroxysalicylaniline (RC17) on the proliferation and apoptosis of T lymphocyte leukemia cells, Jurkat and Hut-78, in vitro and in vivo. Methods: RC17 was used to treat Jurkat and Hut-78 cells with different concentration gradients. CCK8 assay and soft AGAR colony formation assay were used to detect the effect of RC17 on cell proliferation. The cell cycle and cell apoptosis were detected by flow cytometry. Immunofluorescence staining of γ-H2AX was used to detect the DNA damage. Proteins related to cell cycle, apoptosis and DNA damage were detected by Western blot. The mouse T-cell leukemia tumor model was constructed by subcutaneous injection of Jurkat cells, and RC17 was injected to observe the effect of drugs on tumor volume and body weight of mice. HE staining was used to observe the morphological changes of tumors and mouse organs. Immunohistochemical staining of Ki67 and γ-H2AX protein was used to analyze the effect of drugs on cell proliferation and DNA damage in tumors. Results: In Jurkat and Hut-78 cell lines, we demonstrated that RC17 could induce cell cycle arrest at S phase, induce cell apoptosis, and block DNA damage repair through phosphorylation of CHK1/CHK2 signaling pathway, both in vitro and in vivo. RC17 inhibited T cell leukemia tumors, and it had no obvious toxicity to mice. Conclusion: In conclusion, RC17 can be used as a potential anti-T-cell leukemia drug. The effect of RC17 on T-cell leukemia was accomplished through the CHK1/CHK2 signaling pathway.

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  • 收稿日期:2023-03-30
  • 最后修改日期:2023-04-27
  • 录用日期:2023-05-26
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