Effects and mechanism of ursolic acid on malignant biological behavior of human colorectal cancer SW620 cells

SHI Yao; WANG Qing; ZHANG Junhong; HAN Ling; WU Jingjing

doi:10.6039/j.issn.1001-0408.2024.18.11

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Effects and mechanism of ursolic acid on malignant biological behavior of human colorectal cancer SW620 cells

更新时间：2024-09-25

- Effects and mechanism of ursolic acid on malignant biological behavior of human colorectal cancer SW620 cells
- ZHONGGUO YAOFANG Vol. 35, Issue 18, Pages: 2252-2257(2024)
- 作者机构：
  
  1.广州中医药大学第二附属医院脑血管病科，广州　510120
  2.广州中医药大学第二临床医学院，广州　510120
  3.广州中医药大学第二附属医院中医药分子生物与系统生物学研究团队，广州　510120
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.18.11
  CLC： R965
- Published：30 September 2024，
  
  Received：08 April 2024，
  
  Revised：14 August 2024，
- 稿件说明：
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石尧,汪晴,张骏鸿等.熊果酸对人结直肠癌SW620细胞恶性生物学行为的影响及机制 ^Δ[J].中国药房,2024,35(18):2252-2257.

SHI Yao,WANG Qing,ZHANG Junhong,et al.Effects and mechanism of ursolic acid on malignant biological behavior of human colorectal cancer SW620 cells[J].ZHONGGUO YAOFANG,2024,35(18):2252-2257.
石尧,汪晴,张骏鸿等.熊果酸对人结直肠癌SW620细胞恶性生物学行为的影响及机制 ^Δ[J].中国药房,2024,35(18):2252-2257. DOI： 10.6039/j.issn.1001-0408.2024.18.11.

SHI Yao,WANG Qing,ZHANG Junhong,et al.Effects and mechanism of ursolic acid on malignant biological behavior of human colorectal cancer SW620 cells[J].ZHONGGUO YAOFANG,2024,35(18):2252-2257. DOI： 10.6039/j.issn.1001-0408.2024.18.11.

摘要

目的

探讨熊果酸（UA）对人结直肠癌SW620细胞生长、侵袭、凋亡和转移的影响，并研究其可能的分子机制。

方法

以SW620细胞为对象，以CCK-8法检测不同浓度（0、5、10、15、20、25、30 μmol/L）UA作用不同时间（24、48、72 h）对细胞增殖的影响；以克隆形成实验检测不同浓度（0、10、15、20 μmol/L）UA作用于SW620细胞10 d对细胞克隆形成的影响；以不同浓度（0、10、15、20 μmol/L）UA作用于SW620细胞24 h后，分别以流式细胞术、Transwell侵袭实验、Western blot实验检测细胞的凋亡、侵袭情况和细胞中B细胞淋巴瘤2（Bcl-2）、裂解型多腺苷二磷酸核糖聚合酶（cleaved-PARP）、磷酸化p38丝裂原活化蛋白激酶（p-p38 MAPK）、p38 MAPK、上皮钙黏素（E-cadherin）、神经钙黏素（N-cadherin）、锌指转录因子Snail蛋白的表达情况。考察p38 MAPK抑制剂SB203580与UA联用对细胞中p-p38 MAPK、Bcl-2、N-cadherin蛋白表达的影响。

结果

与0 μmol/L UA比较，5～30 μmol/L UA作用24、48、72 h均可显著降低细胞的存活率（

＜0.05）；15、20 μmol/L UA作用10 d均可显著降低细胞的克隆形成率（

＜0.05）；经15、20 μmol/L UA作用后，细胞的凋亡率和cleaved-PARP、E-cadherin蛋白的表达量以及p38 MAPK蛋白的磷酸化水平均升高，穿膜细胞数和Bcl-2、Snail、N-cadherin蛋白的表达量均减少或降低，大部分指标差异有统计学意义（

＜0.05），部分指标变化有浓度依赖性（

＜0.05）。SB203580可显著抑制UA对p38 MAPK蛋白表达的上调作用，逆转UA对Bcl-2、N-cadherin蛋白表达的抑制作用（

＜0.05）。

结论

UA可抑制SW620细胞的生长、侵袭和转移并诱导其凋亡，上述作用可能与激活p38 MAPK信号通路相关。

Abstract

OBJECTIVE

To explore the effects of ursolic acid （UA） on the growth， invasion， apoptosis and metastasis of human colorectal cancer cells SW620 and find out the underlying molecular mechanisms.

METHODS

The effects of different concentrations （0， 5， 10， 15， 20， 25， 30 μmol/L） of UA on the proliferation of SW620 cells for different durations （24， 48， 72 h） were detected by CCK-8 assay； the clone formation was detected by clone formation assay after SW620 cells were treated with different concentrations of UA （0，10，15，20 μmol/L） for 10 days. After SW620 cells were treated with different concentrations of UA （0， 10， 15， 20 μmol/L） for 24 hours， flow cytometry， Transwell invasion assay and Western blot assay were adopted to detect apoptosis and invasion of SW620 cells， and the expressions of B cell lymphoma 2 （Bcl-2）， cleaved-poly （ADP-ribose） polymerase （cleaved-PARP）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， p38 MAPK， E-cadherin， N-cadherin and zinc finger transcription factor Snail. The effects of p38 MAPK inhibitor （SB203580） combined with UA on the protein expressions of p-p38 MAPK， Bcl-2 and N-cadherin were investigated.

RESULTS

Compared with 0 μmol/L UA， the survival rates of SW620 cells treated with 5-30 μmol/L UA for 24， 48 and 72 h were significantly decreased （

＜0.05）. The clone formation rate of cells treated with 15 μmol/L and 20 μmol/L UA was significantly decreased （

＜0.05）. After being treated with 15 μmol/L and 20 μmol/L UA， the cell apoptosis rate， the protein expressions of cleaved-PARP and E-cadherin， and the phosphorylation of p38 MAPK protein were increased； but the number of transmembrane cells， and the protein expressions of Bcl-2， Snail and N-cadherin were decreased； there was statistical significance in difference of most indexes （

＜0.05）. Some indexes changed in a concentration-dependent manner （

＜0.05）. SB203580 could significantly inhibit the upregulation of p38 MAPK by UA and reverse the inhibitory effect of UA on the protein expressions of Bcl-2 and N-cadherin （

＜0.05）.

CONCLUSIONS

UA can inhibit the growth， invasion and metastasis of SW620 cells， and induce cell apoptosis， the mechanism of which may be attributed to the activation of p38 MAPK signaling pathway.

关键词

熊果酸人结直肠癌生长侵袭转移凋亡p38丝裂原活化蛋白激酶

Keywords

human colorectal cancergrowthinvasionmetastasisapoptosisp38 MAPK

references

SUNG H，FERLAY J，SIEGEL R L，et al. Global cancer statistics 2020：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin，2021，71（3）：209-249.

ABEDIZADEH R，MAJIDI F，KHORASANI H R，et al. Colorectal cancer：a comprehensive review of carcinoge-nesis，diagnosis，and novel strategies for classified treatments[J]. Cancer Metastasis Rev，2024，43（2）：729-753.

陈燕，何沙，陈春林. 熊果酸药理作用研究进展[J]. 宜春学院学报，2023，45（9）：21-26.

CHEN Y，HE S，CHEN C L. Research progress on the pharmacological effects of ursolic acid[J]. J Yichun Univ，2023，45（9）：21-26.

ZHANG M Z，XIANG F F，SUN Y P，et al. Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression[J]. Oncol Rep，2024，51（2）：27.

ALAM M，ALI S，AHMED S，et al. Therapeutic potential of ursolic acid in cancer and diabetic neuropathy diseases[J]. Int J Mol Sci，2021，22（22）：12162.

ZHU Z L，QIAN Z Z，YAN Z，et al. A phase Ⅰ pharmacokinetic study of ursolic acid nanoliposomes in healthy vo-lunteers and patients with advanced solid tumors[J]. Int J Nanomedicine，2013，8：129-136.

GARCÍA-HERNÁNDEZ L，GARCÍA-ORTEGA M B，RUIZ-ALCALÁ G，et al. The p38 MAPK components and modulators as biomarkers and molecular targets in cancer[J]. Int J Mol Sci，2021，23（1）：370.

XUE Q，WANG X B，WANG P，et al. Role of p38 MAPK in apoptosis and autophagy responses to photodynamic therapy with Chlorin e6[J]. Photodiagnosis Photodyn Ther，2015，12（1）：84-91.

NEWMAN D J，CRAGG G M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019[J]. J Nat Prod，2020，83（3）：770-803.

LÓPEZ-HORTAS L，PÉREZ-LARRÁN P，GONZÁLEZ-MUÑOZ M J，et al. Recent developments on the extraction and application of ursolic acid： a review[J]. Food Res Int，2018，103：130-149.

LIAN M Q，CHNG W H，LIANG J，et al. Plant-derived extracellular vesicles：recent advancements and current challenges on their use for biomedical applications[J]. J Extracell Vesicles，2022，11（12）：e12283.

KIM C，KIM B. Anti-cancer natural products and their bioactive compounds inducing ER stress-mediated apoptosis：a review[J]. Nutrients，2018，10（8）：1021.

EMDAD L，BHOOPATHI P，TALUKDAR S，et al. Recent insights into apoptosis and toxic autophagy：the roles of MDA-7/IL-24，a multidimensional anti-cancer therapeutic[J]. Semin Cancer Biol，2020，66：140-154.

LI C Y，CHEN H B，CHEN X J，et al. Identification of inflammatory response-related molecular mechanisms based on the ATM/ATR/p53 pathway in tumor cells[J]. Comput Biol Med，2024，180：108776.

于菲，罗卓，黎骊，等. 氯化两面针碱通过PI3K/Akt/Bcl-2/caspase-3/PARP通路诱导小细胞肺癌细胞H1688和H446凋亡[J]. 中国药理学通报，2022，38（7）：1023-1031.

YU F，LUO Z，LI L，et al. Apoptosis of small cell lung cancer cells H1688 and H446 induced by nitidine chloride through PI3K/Akt/Bcl-2/caspase-3/PARP pathway[J]. Chin Pharmacol Bull，2022，38（7）：1023-1031.

DE SANTANA D A，BRAGA P R，CAMILLO-COUTINHO C M，et al. E-caderin，N-caderin，Slug，Snail，and Twist contribute to epithelial-mesenchymal transition in salivary gland tumors[J]. J Oral Pathol Med，2024，53（3）：193-200.

JIA X B，ZHANG Q，XU L，et al. Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway[J]. Biol Res，2021，54（1）：7.

DAI Z Y，XIE B，YANG B S，et al. KANK3 mediates the p38 MAPK pathway to regulate the proliferation and invasion of lung adenocarcinoma cells[J]. Tissue Cell，2023，80：101974.

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