阿魏酸通过调节PTEN/PI3K/AKT信号通路抑制急性T淋巴细胞白血病进展

李敬茹; 李中霞; 牛宁宁; 乔缘; 韩芸; 林雪容

doi:10.11659/jjssx.10E022056

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阿魏酸通过调节PTEN/PI3K/AKT信号通路抑制急性T淋巴细胞白血病进展

基础研究 | 更新时间：2024-01-22

- 阿魏酸通过调节PTEN/PI3K/AKT信号通路抑制急性T淋巴细胞白血病进展
- Ferulic acid inhibits the progression of T-cell acute lymphoblastic leukemia by regulating PTEN/PI3K/AKT signaling pathway
- 局解手术学杂志 2024年33卷第1期页码：8-13
- 作者机构：
  
  河北北方学院附属第一医院急诊科，河北张家口 075000
- 作者简介：
  
  李敬茹，E-mail：15731332236@163.com
- 基金信息：
  
  2021年度河北省医学科学研究课题计划(20211689)
- DOI：10.11659/jjssx.10E022056
  中图分类号： R733.71
- 纸质出版日期：2024-01-25，
  
  收稿日期：2022-10-13，
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李敬茹,李中霞,牛宁宁等.阿魏酸通过调节PTEN/PI3K/AKT信号通路抑制急性T淋巴细胞白血病进展[J].局解手术学杂志,2024,33(01):8-13.

LI Jing-ru,LI Zhong-xia,NIU Ning-ning,et al.Ferulic acid inhibits the progression of T-cell acute lymphoblastic leukemia by regulating PTEN/PI3K/AKT signaling pathway[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(01):8-13.
李敬茹,李中霞,牛宁宁等.阿魏酸通过调节PTEN/PI3K/AKT信号通路抑制急性T淋巴细胞白血病进展[J].局解手术学杂志,2024,33(01):8-13. DOI： 10.11659/jjssx.10E022056.

LI Jing-ru,LI Zhong-xia,NIU Ning-ning,et al.Ferulic acid inhibits the progression of T-cell acute lymphoblastic leukemia by regulating PTEN/PI3K/AKT signaling pathway[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(01):8-13. DOI： 10.11659/jjssx.10E022056.

摘要

目的

探究阿魏酸是否可通过调控PTEN/PI3K/AKT信号通路在体内外抑制急性T淋巴细胞白血病进展。

方法

将急性T淋巴细胞白血病Jurkat细胞分为对照组、阿魏酸处理组和LY294002处理组进行体外实验，对照组正常培养；阿魏酸处理组分别给予不同浓度（1.25、2.5、5、10、20、40、80、160 μmol/L）阿魏酸，采用CCK-8法检测细胞增殖能力，筛选实验浓度；LY294002处理组给予50 μmol/L PI3K/AKT抑制剂LY294002，采用克隆形成实验、流式细胞术、Transwell实验检测细胞增殖、凋亡、侵袭情况，采用Western blot检测核蛋白Ki67、增殖细胞核抗原（PCNA）、cleaved caspase-3、cleaved caspase-9、E-cadherin、N-cadherin、Vimentin、PTEN、p-PI3K、PI3K、p-AKT和AKT蛋白相对表达量。使用30只雄性BALB/c裸鼠建立移植瘤裸鼠模型，平均分为正常组和阿魏酸处理组进行体内实验，正常组接种Jurkat细胞后以生理盐水灌胃，阿魏酸处理组接种Jurkat细胞后以75 mg/kg阿魏酸灌胃，比较移植瘤质量和体积变化，并检测肿瘤组织中Ki67、cleaved caspase-3/caspase-3、E-cadherin、N-cadherin、PTEN、p-PI3K、PI3K、p-AKT和AKT水平。

结果

体外实验中，与对照组比较，5、10、20 μmol/L阿魏酸处理组和LY294002处理组细胞克隆形成率、细胞侵袭数、Ki67、PCNA、N-cadherin、Vimentin、p-PI3K/PI3K、p-AKT/AKT明显降低/减少（

0.05），细胞凋亡率、cleaved caspase-3/caspase-3、cleaved caspase-9/caspase-9、E-cadherin、PTEN明显升高（

0.05）。体内实验中，与正常组比较，阿魏酸处理组裸鼠肿瘤质量减轻，肿瘤体积减小，肿瘤组织中Ki67、N-cadherin、p-PI3K/PI3K、p-AKT/AKT明显降低，cleaved caspase-3/caspase-3、E-cadherin、PTEN明显升高，差异均有统计学意义（

0.05）。

结论

阿魏酸在体内外均可抑制急性T淋巴细胞白血病Jurkat细胞的增殖及侵袭，并诱导细胞凋亡，其作用机制可能与调控PTEN/PI3K/AKT信号通路有关。

Abstract

Objective

To explore whether ferulic acid can inhibit the progression of T-cell acute lymphoblastic leukemia in vivo and in vitro by regulating PTEN/PI3K/AKT signaling pathway.

Methods

The T-cell acute lymphoblastic leukemia Jurkat cells were divided into the control group，the ferulic acid treatment group and the LY294002 treatment group for in vitro experiment. The cells in the control group were given normal culture；cells in the ferulic acid treatment group were given different concentrations （1.25，2.5，5，10，20，40，80，160 μmol/L） of ferulic acid，respectively，and the cell proliferation was detected by CCK-8 method，to screen the experimental concentration；cells in the LY294002 treatment group were given 50 μmol/L PI3K/AKT inhibitor LY294002.The cells proliferation， apoptosis and invasion were detected by clone formation assay，flow cytometry and Transwell assay.The relative expression levels of nuclear protein Ki67，proliferating cell nuclear antigen （PCNA），cleaved caspase-3，cleaved caspase-9，E-cadherin，N-cadherin，Vimentin，PTEN，p-PI3K，PI3K，p-AKT and AKT proteins were detected by Western blot.The nude mice models of transplanted tumors were constructed by 30 male BALB/c nude mice， and they were averagely divided into the normal group and the ferulic acid treatment group for in vivo experiment.The normal group was given normal saline by gavage，while the ferulic acid treatment group was given 75 mg/kg ferulic acid by gavage after inoculating Jurkat cells.The weight and volume changes of transplanted tumors were compared，and the levels of Ki67，cleaved caspase-3/caspase-3，E-cadherin，N-cadherin，PTEN，p-PI3K，PI3K，p-AKT and AKT in tumor tissues were detected.

Results

In vitro experiment，compared with the control group，the clone formation rate of cells，number of invasion cells，Ki67，PCNA，N-cadherin，Vimentin，p-PI3K/PI3K and p-AKT/AKT in the 5，10，20 μmol/L ferulic acid treatment group and the LY294002 treatment group were significantly decreased（

0.05），while the apoptosis rate，cleaved caspase-3/caspase-3，cleaved caspase-9/caspase-9，E-cadherin and PTEN were significantly increased（

0.05）.In vivo experiment，compared with the normal group，the weight and volume of tumors were reduced in the ferulic acid treatment group，Ki67，N-cadherin，p-PI3K/PI3K and p-AKT/AKT in tumor tissues were significantly decreased，cleaved caspase-3/caspase-3，E-cadherin and PTEN were significantly increased，with statistically significant differences（

0.05）.

Conclusion

Ferulic acid can inhibit the proliferation and invasion of T-cell acute lymphoblastic leukemia Jurkat cells in vivo and in vitro，and induce apoptosis，its mechanism may be related to the regulation of PTEN/PI3K/AKT signaling pathway.

关键词

急性T淋巴细胞白血病阿魏酸PTEN/PI3K/AKT信号通路增殖凋亡侵袭

Keywords

T-cell acute lymphoblastic leukemiaferulic acidPTEN/PI3K/AKT signaling pathwayproliferationapoptosisinvasion

references

Pui CH.Precision medicine in acute lymphoblastic leukemia［J］.Front Med，2020，14（6）：689-700.doi：10.1007/s11684-020-0759-8http://dx.doi.org/10.1007/s11684-020-0759-8.

Samra B，Jabbour E，Ravandi F，et al.Evolving therapy of adult acute lymphoblastic leukemia：state-of-the-art treatment and future directions［J］.J Hematol Oncol，2020，13（1）：70.doi：10.1186/s13045-020-00905-2http://dx.doi.org/10.1186/s13045-020-00905-2.

刘慧敏，刘斌，李国强，等.阿魏酸对慢性阻塞性肺疾病小鼠肺功能的影响及作用机制研究［J］.中国中西医结合急救杂志，2019，26（5）：560-563.doi：10.3969/j.issn.1008-9691.2019.05.012http://dx.doi.org/10.3969/j.issn.1008-9691.2019.05.012.

Al-Mutairi A，Rahman A，Rao MS.Low doses of thymoquinone and ferulic acid in combination effectively inhibit proliferation of cultured MDA-MB 231 breast adenocarcinoma cells［J］.Nutr Cancer，2021，73（2）：282-289.doi：10.1080/01635581.2020.1743869http://dx.doi.org/10.1080/01635581.2020.1743869.

郭风，赵瑞敏，李景亮，等.阿魏酸通过调控JAK2/STAT6免疫信号通路抑制肺癌细胞增殖和转移［J］.中国免疫学杂志，2021，37（4）：459-462.doi：10.3969/j.issn.1000-484X.2021.04.015http://dx.doi.org/10.3969/j.issn.1000-484X.2021.04.015.

Thakkar A，Chenreddy S，Wang J，et al.Ferulic acid combined with aspirin demonstrates chemopreventive potential towards pancreatic cancer when delivered using chitosan-coated solid-lipid nanoparticles［J］.Cell Biosci，2015，5（1）：46.doi：10.1186/s13578-015-0041-yhttp://dx.doi.org/10.1186/s13578-015-0041-y.

尹婕，李琦，孙立东，等.天然产物抗癌研究进展［J］.中国中药杂志，2019，44（1）：27-35.doi：10.19540/j.cnki.cjcmm.20181 107.001http://dx.doi.org/10.19540/j.cnki.cjcmm.20181107.001.

Lambruschini C，Demori I，Rashed ZE，et al.Synthesis，photoisomerization，antioxidant activity，and lipid-lowering effect of ferulic acid and feruloyl amides［J］.Molecules，2020，26（1）：89.doi：10.3390/molecules26010089http://dx.doi.org/10.3390/molecules26010089.

毛广显，刘继先，鲁建军.阿魏酸通过调节相关信号通路诱导食管癌细胞周期阻滞和自噬的发生［J］.中华实验外科杂志，2020，37（9）：1665-1668.doi：10.3760/cma.j.cn421213-20200323-00178http://dx.doi.org/10.3760/cma.j.cn421213-20200323-00178.

Yue SJ，Zhang PX，Zhu Y，et al.A ferulic acid derivative FXS-3 inhibits proliferation and metastasis of human lung cancer A549 cells via positive JNK signaling pathway and negative ERK/p38，AKT/mTOR and MEK/ERK signaling pathways［J］.Molecules，2019，24（11）：2165.doi：10.3390/molecules24112165http://dx.doi.org/10.3390/molecules24112165.

Liu X，Zhou C，Li Y，et al.Upregulation of circ-0000745 in acute lymphoblastic leukemia enhanced cell proliferation by activating ERK pathway［J］.Gene，2020，751：144726.doi：10.1016/j.gene.2020. 144726http://dx.doi.org/10.1016/j.gene.2020.144726.

Rashidbaghan A，Mostafaie A，Yazdani Y，et al.Urtica dioica agglutinin （a plant lectin） has a caspase-dependent apoptosis induction effect on the acute lymphoblastic leukemia cell line［J］.Cell Mol Biol （Noisy-le-grand），2020，66（6）：121-126.

蒋海兵，王伟，盘箐，等.自噬相关蛋白4A对胃癌细胞干性及上皮间质转化的影响［J］.实用医学杂志，2019，35（16）：23-28.doi：10.3969/j.issn.1006-5725.2019.16.004http://dx.doi.org/10.3969/j.issn.1006-5725.2019.16.004.

Xu F，Na L，Li Y，et al.Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours［J］.Cell Biosci，2020，10（1）：54.doi：10.1186/s13578-020-00416-0http://dx.doi.org/10.1186/s13578-020-00416-0.

杜趁香，王焱，武海英.过表达miR-141-3p通过靶向下调PTEN并激活PI3K/Akt信号通路促进卵巢癌A2780细胞的恶性生物学行为［J］.中国肿瘤生物治疗杂志，2019，26（5）：563-568.doi：10.3872/j.issn.1007-385x.2019.05.013http://dx.doi.org/10.3872/j.issn.1007-385x.2019.05.013.

Gehringer F，Weissinger SE，Mller P，et al.Physiological levels of the PTEN-PI3K-AKT axis activity are required for maintenance of Burkitt lymphoma［J］.Leukemia，2019，34（25）：857-871.doi：10.1038/s41375-019-0628-0http://dx.doi.org/10.1038/s41375-019-0628-0.

Tottone L，Lancho O，Loh JW，et al.A tumor suppressor enhancer of PTEN in T-cell development and leukemia［J］.Blood Cancer Discov，2021，2（1）：92-109.doi：10.1158/2643-3230.BCD-20-0201http://dx.doi.org/10.1158/2643-3230.BCD-20-0201.

Meng J，Liu GJ，Song JY，et al.Preliminary results indicate resveratrol affects proliferation and apoptosis of leukemia cells by regulating PTEN/PI3K/AKT pathway［J］.Eur Rev Med Pharmacol Sci，2019，23（10）：4285-4292.doi：10.26355/eurrev_201905_17933http://dx.doi.org/10.26355/eurrev_201905_17933.

Luo L，Zhu S，Tong Y，et al.Ferulic acid induces apoptosis of HeLa and Caski cervical carcinoma cells by down-regulating the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway［J］.Med Sci Monit，2020，26：e920095.doi：10.12659/MSM.920095http://dx.doi.org/10.12659/MSM.920095.

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