[1]冯阳,王飞,蒲柯.白杨素协同调控Alox12-GPX4/Bcl-2轴激活铁死亡抑制结直肠癌SW480细胞增殖、迁移、凋亡实验研究[J].陕西医学杂志,2026,(3):291-298.[doi:DOI:10.3969/j.issn.1000-7377.2026.03.001]
　FENG Yang,WANG Fei,PU Ke.CHR activates ferroptosis to inhibit proliferation,migration,and induce apoptosis in colorectal cancer SW480 cells by co-regulating Alox12-GPX4/Bcl-2 Axis[J].,2026,(3):291-298.[doi:DOI:10.3969/j.issn.1000-7377.2026.03.001]
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白杨素协同调控Alox12-GPX4/Bcl-2轴激活铁死亡抑制结直肠癌SW480细胞增殖、迁移、凋亡实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年3期
页码:
291-298
栏目:
基础研究
出版日期:
2026-03-05

文章信息/Info

Title:
CHR activates ferroptosis to inhibit proliferation,migration,and induce apoptosis in colorectal cancer SW480 cells by co-regulating Alox12-GPX4/Bcl-2 Axis
作者:
冯阳1; 王飞2; 蒲柯2
（1.西北大学附属医院 西安市第三医院，陕西 西安 710018；2.川北医学院附属医院，四川 南充 637000）
Author(s):
FENG Yang1; WANG Fei2; PU Ke2
(1.Affiliated Hospital of Northwest University,Xi’an 710018,China;2.Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China)
关键词:
结直肠癌; 白杨素; 铁死亡; 花生四烯酸脂氧合酶12; 凋亡; 脂质过氧化; 谷胱甘肽过氧化物酶4
Keywords:
Colorectal cancer; Chrysin; Ferroptosis; Arachidonate lipoxygenase 12; Apoptosis; Lipid peroxidation; Glutathione peroxidase 4
分类号:
R 285.5
DOI:
DOI:10.3969/j.issn.1000-7377.2026.03.001
文献标志码:
A
摘要:
目的：探讨白杨素（CHR）调节花生四烯酸脂氧合酶12（Alox12）-谷胱甘肽过氧化物酶4（GPX4）/B细胞淋巴瘤-2（Bcl-2）轴激活铁死亡对结直肠癌（CRC）SW480细胞增殖、迁移、凋亡的影响。方法：基于网络药理学筛选CHR作用靶点，通过分子对接验证其与Alox12的结合能力。体外细胞实验中，采用CCK-8法筛选适合的药物作用浓度；将对数生长期SW480细胞分为NC组及20、60 μmol/LCHR组，采用平板划痕实验评估迁移能力，采用Western blot检测GPX4、Bcl-2蛋白表达，采用实时荧光定量PCR（RT-qPCR）分析Alox12 mRNA水平。结果：获得6个铁死亡-CHR-CRC交集靶点，结合蛋白质互作网络分析及分子对接确定Alox12为CHR治疗CRC的核心靶点。体外实验中，与NC组比较，60 μmol/L CHR组CRC细胞存活率、横向迁移能力被抑制，铁死亡相关蛋白GPX4和抗凋亡蛋白Bcl-2表达水平下调（均P＜0.05），而20 μmol/LCHR组与NC组上述指标比较差异无统计学意义（均P＞0.05）；与NC组比较，60 μmol/L CHR组上调了Alox12 mRNA表达（P＜0.05）。结论：CHR可抑制SW480细胞增殖与迁移，其机制可能与抑制GPX4/Bcl-2进而激活铁死亡-凋亡交叉调控网络和靶向调控Alox12有关。
Abstract:
Objective:To investigate the effects of chrysin (CHR) on proliferation,migration,and apoptosis of colorectal cancer (CRC) cells SW480 by regulating the arachidonate 12-lipoxygenase (Alox12)-glutathione peroxidase 4 (GPX4)/B-cell lymphoma-2 (Bcl-2) axis to activate ferroptosis.Methods：Potential targets of CHR were screened using network pharmacology,and molecular docking was employed to validate its binding affinity with Alox12.In the in vitro experiments,the CCK-8 assay was employed to determine the optimal drug concentrations.SW480 cells in the logarithmic growth phase were divided into the following groups：negative control (NC) group,and groups treated with 20,60 μmol/L of CHR.A wound healing assay was conducted to evaluate cell migration capability.The protein expression levels of GPX4 and Bcl-2 were detected by Western blot,while the mRNA level of Alox12 was analyzed using RT-qPCR.Results:Six overlapping targets related to ferroptosis,CHR,and CRC were identified.Combined with protein-protein interaction network analysis and molecular docking,Alox12 was determined as the core target of CHR in the treatment of CRC.In vitro,compared to the NC group,treatment with 60 μmol/L CHR significantly inhibited the survival and horizontal migration of CRC cells,and downregulated the expression of the ferroptosis-related protein GPX4 and the anti-apoptotic protein Bcl-2 (all P<0.05).In contrast,the 20 μmol/L CHR group showed no statistically significant differences in these indicators compared to the control group (all P>0.05).Furthermore,the 60 μmol/L CHR treatment significantly increased the mRNA expression of Alox12 compared to the NC group (P<0.05).Conclusion:CHR can inhibit the proliferation and migration of CRC cells,and the underlying mechanism may be associated with the suppression of GPX4/Bcl-2,thereby activating the ferroptosis-apoptosis crossover network and targeting the regulation of Alox12.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82204877）；西安市科协青年人才托举计划项目（959202313026）
更新日期/Last Update: 2026-03-05