Effects of galangin on proliferation,apoptosis and 5-FU resistance of colorectal cancer cells by regulating FOXO3-FOXM1 axis

YANG Liu; FENG Dan; YANG Li; TANG Ling; LUO Fei

doi:10.11659/jjssx.01E024030

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Effects of galangin on proliferation,apoptosis and 5-FU resistance of colorectal cancer cells by regulating FOXO3-FOXM1 axis

Basic Research | 更新时间：2025-01-16

- Effects of galangin on proliferation,apoptosis and 5-FU resistance of colorectal cancer cells by regulating FOXO3-FOXM1 axis
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 34, Issue 1, Pages: 5-10(2025)
- 作者机构：
  
  川北医学院附属医院药剂科，四川南充 637000
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.01E024030
  CLC： R735.3
- Published：25 January 2025，
  
  Received：08 January 2024，
- 稿件说明：
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YANG LIU, FENG DAN, YANG LI, et al. Effects of galangin on proliferation,apoptosis and 5-FU resistance of colorectal cancer cells by regulating FOXO3-FOXM1 axis. [J]. Journal of regional anatomy and operative surgery, 2025, 34(1): 5-10.
DOI：

YANG LIU, FENG DAN, YANG LI, et al. Effects of galangin on proliferation,apoptosis and 5-FU resistance of colorectal cancer cells by regulating FOXO3-FOXM1 axis. [J]. Journal of regional anatomy and operative surgery, 2025, 34(1): 5-10. DOI： 10.11659/jjssx.01E024030.

摘要

目的

探讨高良姜素调节FOXO3-FOXM1轴对结直肠癌（CRC）细胞增殖、凋亡和5-氟尿嘧啶（5-FU）耐药性的影响。

方法

体外培养CRC细胞HCT8及其耐药细胞株HCT8/5-FU，然后用不同浓度（0、5、10、20、40 µmol/L）的高良姜素处理，筛选实验浓度。将HCT8细胞分为ctrl组（不进行特殊处理）、NC组（转染空载质粒）、L-高良姜素组（10 μmol/L高良姜素处理）、H-高良姜素组（20 μmol/L高良姜素处理）、H-高良姜素+sh-FOXO3组（20 μmol/L高良姜素处理后转染FOXO3 shRNA质粒）。将HCT8/5-FU细胞分为对照组（不做特殊处理）、5-FU＋NC组（5 µg/mL 5-FU处理后转染空载质粒）、5-FU组（5 µg/mL 5-FU处理）、5-FU+L-高良姜素组（5 µg/mL 5-FU处理后加入10 μmol/L高良姜素）、5-FU+H-高良姜素组（5 µg/mL 5-FU处理后加入20 μmol/L高良姜素）、5-FU+H-高良姜素+sh-FOXO3组（经5 μg/mL 5-FU和20 μmol/L高良姜素处理后，再转染FOXO3 shRNA质粒）。CCK-8法检测细胞的增殖能力；克隆形成实验检测细胞克隆形成能力；流式细胞术检测细胞凋亡水平；Western blot检测相关蛋白表达。

结果

在HCT8细胞中，与0 μmol/L高良姜素处理比较，10、20、40 μmol/L高良姜素处理会降低细胞存活率（

0.05）；在HCT8/5-FU细胞中，与0 μmol/L高良姜素处理比较，40 μmol/L高良姜素处理可降低细胞存活率（

0.05）。在HCT8和HCT8/5-FU细胞中，10、20 μmol/L高良姜素干预后细胞凋亡率、FOXO3和Bax蛋白表达升高（

0.05），而细胞存活率、克隆形成数、FOXM1和PCNA蛋白表达降低/减少（

0.05），HCT8/5-FU细胞中MRP-1蛋白表达降低（

0.05）。敲低FOXO3可减弱高剂量高良姜素对HCT8和HCT8/5-FU细胞的作用（

0.05）。

结论

高良姜素可能通过调节FOXO3-FOXM1轴抑制CRC细胞的增殖，促进细胞凋亡，并降低细胞对5-FU的耐药性。

Abstract

Objective

To investigate the effects of galangin on the proliferation，apoptosis，and 5-fluorouracil （5-FU） resistance of colorectal cancer （CRC） cells by regulating the FOXO3-FOXM1 axis.

Methods

CRC cells HCT8 and its drug-resistant cell lines HCT8/5-FU were cultured in vitro，and then treated with different concentrations （0，5，10，20，40 µmol/L） of galangin to screen experimental concentrations. HCT8 cells were divided into the ctrl group （without special treatment），NC group （transfected with empty plasmid），L-galangin group （treated with 10 μmol/L of galangin ），H-galangin group （treated with 20 μmol/L of galangin），and H-galangin+sh-FOXO3 group （transfected with FOXO3 shRNA plasmid after 20 μmol/L of galangin treatment）. HCT8/5-FU cells were divided into the control group （without special treatment），5-FU+NC group （treated with empty plasmid after 5 µg/mL of 5-FU treatment），5-FU group （treated with 5 µg/mL of 5-FU），5-FU+L-galangin group （treated with 10 μmol/L of galangin after 5 µg/mL of 5-FU treatment），5-FU+H-galangin group （transfected with 20 μmol/L galangin after 5 µg/mL of 5-FU treatment），and 5-FU+H-galangin+sh-FOXO3 group （transfected with FOXO3 shRNA plasmid after 5 µg/mL of 5-FU and 20 μmol/L of galangin treatment）. The cell proliferation ability was detected by CCK-8 assay； the cell clone formation ability was detected by clone formation assay； the cell apoptosis was detected by flow cytometry ； the expression of related proteins were detected by Western blot.

Results

In HCT8 cells，compared with 0 µmol/L of galangin treatment，10，20，40 µmol/L of galangin treatment decreased the cell survival rate （

0.05）. In HCT8/5-FU cells，compared with 0 µmol/L galangin treatment，40 µmol/L of galangin treatment decreased the cell survival rate （

0.05）. After 10 and 20 µmol/L of galangin treatment，the apoptosis rate，and the expression of FOXO3 and Bax proteins were increased （

0.05），while ce

ll survival rate，clone formation number，and expression of FOXM1 and PCNA proteins decreased in HCT8 and HCT8/5-FU cells （

0.05），and the MRP-1 protein expression in HCT8/5-FU cells decreased （

0.05）. Knocking down sh-FOXO3 could attenuate the effects of high dose of galangin on HCT8 and HCT8/5-FU cells （

0.05）.

Conclusion

Galangin may inhibit the proliferation，promote apoptosis，and reduce 5-FU resistance of CRC cells by regulating the FOXO3-FOXM1 axis.

关键词

高良姜素FOXO3-FOXM1轴结直肠癌增殖凋亡5-氟尿嘧啶耐药性

Keywords

galanginFOXO3-FOXM1 axiscolorectal cancerproliferationapoptosis5-fluorouracilresistance

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