金缕半枫荷的水提取物抑制胰腺癌的作用机制：活性成分、关键靶点和信号通路

doi:10.12122/j.issn.1673-4254.2024.07.13

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (7): 1336-1344.doi: 10.12122/j.issn.1673-4254.2024.07.13

金缕半枫荷的水提取物抑制胰腺癌的作用机制：活性成分、关键靶点和信号通路

黄燕¹(), 覃璐璐¹, 管少兴², 管宴萍², 韦玉茹², 操艾伶², 李冬梅³, 韦桂宁³(), 苏启表¹()

^1.广东药科大学健康学院，广东广州 510006
^2.中山大学药学院，广东广州 510060
^3.广西壮族自治区中医药研究院广西中药质量标准研究重点实验室，广西南宁 530022

收稿日期:2023-12-21 出版日期:2024-07-20 发布日期:2024-07-25
通讯作者: 韦桂宁,苏启表 E-mail:211214003@gdpu.edu.cn;weiguining2013@163.com;suqibiao@163.com
作者简介:黄燕，在读硕士研究生，E-mail: 211214003@gdpu.edu.cn
基金资助:
国家自然科学基金(81703769);广西人才基地项目(AD22035055);广东省自然科学基金(2019A1515011669)

Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways

Yan HUANG¹(), Lulu QIN¹, Shaoxing GUAN², Yanping GUANG², Yuru WEI², Ailing CAO², Dongmei LI³, Guining WEI³(), Qibiao SU¹()

^1.College of Health Science, Guangdong Pharmaceutical University, Guangzhou 510006, China
^2.School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510060, China
^3.Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Nanning 530022, China

Received:2023-12-21 Online:2024-07-20 Published:2024-07-25
Contact: Guining WEI, Qibiao SU E-mail:211214003@gdpu.edu.cn;weiguining2013@163.com;suqibiao@163.com
Supported by:
National Natural Science Foundation of China(81703769)

摘要/Abstract

摘要：

目的采用网络药理学及分子对接技术预测金缕半枫荷抗胰腺癌的关键靶点及信号通路，并通过胰腺癌细胞模型验证金缕半枫荷抗胰腺癌作用机制。方法通过网络药理学数据库预测药物及疾病的靶点，构建蛋白互作网络图，分析通路、功能富集和分子对接。通过CCK-8法筛选金缕半枫荷对8种癌细胞的活性，并采用侵袭、迁徙、增殖、凋亡实验方法验证金缕半枫荷对胰腺癌的作用。采用Western blotting验证网络药理学的结果。结果网络药理学共筛选得到金缕半枫荷活性成分18个，调控胰腺癌的潜在关键靶点21个。生物富集结果主要与蛋白质的磷酸化、信号传导、细胞凋亡等有关，通路主要与癌症信号通路、PI3K-Akt信号通路等有关。金缕半枫荷对胰腺癌细胞最敏感且显著抑制胰腺癌细胞Panc-1侵袭、迁徙和增殖，并且促进细胞凋亡（P<0.05）。Western blotting结果表明金缕半枫荷可以显著抑制PI3K和AKT的磷酸化水平（P<0.001）。结论金缕半枫荷通过多成分、多靶点、多通路发挥抗胰腺癌作用，其中抑制PI3K-Akt通路是其机制之一。

关键词: 金缕半枫荷, 胰腺癌, 网络药理学, 分子对接, 通路分析

Abstract:

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang (SC) root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments. Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database, the protein-protein interaction network was constructed, and pathways, functional enrichment and molecular docking analyses were performed. CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines, and its effects on invasion, migration, proliferation, and apoptosis of pancreatic cancer cells were evaluated. Western blotting was performed to verify the results of network pharmacology analysis. Results We identified a total of 18 active components in SC, which regulated 21 potential key targets in pancreatic cancer. GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation, signal transduction, and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways. Among the 8 cancer cell lines, The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells, and significantly inhibited the invasion, migration, and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells (P<0.05). Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells (P<0.001). Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Key words: Semiliquidambar cathayensis Chang, pancreatic cancer, network pharmacology, molecular docking, pathway analysis

黄燕, 覃璐璐, 管少兴, 管宴萍, 韦玉茹, 操艾伶, 李冬梅, 韦桂宁, 苏启表. 金缕半枫荷的水提取物抑制胰腺癌的作用机制：活性成分、关键靶点和信号通路[J]. 南方医科大学学报, 2024, 44(7): 1336-1344.

Yan HUANG, Lulu QIN, Shaoxing GUAN, Yanping GUANG, Yuru WEI, Ailing CAO, Dongmei LI, Guining WEI, Qibiao SU. Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways[J]. Journal of Southern Medical University, 2024, 44(7): 1336-1344.

图/表 8

图1 金缕半枫荷和5-氟尿嘧啶对癌细胞的IC50

Fig.1 IC50 of Semiliquidambar cathayensis Chang root extract (SC) and 5-fluorouracil for different cancer cell lines. A-H: IC50 of Semiliquidambar cathayensis Chang against T98G, MCF-7, HePG2, Panc-1, A549, HCT116, A375, and NCI-H1299 cells; I: IC50 of 5-FU against Panc-1 cells.

表1 金缕半枫荷的主要活性成分

Tab.1 Main active components in Semiliquidambar cathayensis Chang root

Ingredient	CAS	Degree
Quercetin	117-39-5	52
Kaempferol	520-18-3	51
Naringenin	480-41-1	50
2,3,8-Tri-O-methylellagic acid	1617-49-8	31
Oleanolic acid	508-02-1	29
Paeoniflorin	23180-57-6	27
Bergaptol	486-60-2	26
Palmitic acid	57-10-3	25
Fraxin	524-30-1	20
Beta-Sitosterol	83-46-5	17
Songorine	509-24-0	16
Atractylenolide-1	73069-13-3	14
Daucosterol	474-58-8	14
Hyperoside	482-36-0	11
Gallic acid	149-91-7	10
Isoquercitrin	21637-25-2	9
Rutin	153-18-4	9
Acteoside(Verbascoside)	61276-17-3	5

图2 金缕半枫荷靶点与胰腺癌靶点韦恩图

Fig.2 Venn diagram of the targets of Semiliquidambar cathayensis Chang and pancreatic cancer.

图3 金缕半枫荷关键成分预测

Fig.3 Prediction of the key components of Semiliquidambar cathayensis Chang. The circles indicate the target points of the intersection targets, and the V-shaped marks are the chemical components of Semiliquidambar cathayensis Chang. A darker color indicates a larger degree value.

图4 金缕半枫荷与胰腺癌关键靶点预测

Fig.4 Prediction of the key targets of Semiliquidambar cathayensis Chang and pancreatic cancer. The V-shaped marks indicate the key targets of Semiliquidambar cathayensis Chang, and the circles are other target points. A darker color indicates a larger degree value.

图5 金缕半枫荷抗胰腺癌的GO分析

Fig.5 GO analysis of the therapeutic mechanism of Semiliquidambar cathasis Chang against pancreatic cancer.

图6 金缕半枫荷抗胰腺癌的KEGG分析

Fig.6 KEGG analysis of the therapeutic mechanism of Semiliquidambar cathasis Chang against pancreatic cancer.

表2 关键成分与关键靶点的对接分数

Tab.2 Molecular docking score of the key components against the key targets

Affinity	Naringenin	2, 3, 8-Tri-O-methylellagic acid	Quercetin	Kaempferol	Oleanolic acid
HSP90AA1	-8.9	-9.3	-9.3	-9.4	-7.0
SRC	-8.3	-7.9	-8.8	-8.6	-9.1
STAT3	-7.7	-7.2	-8.1	-7.8	-6.9
PIK3R1	-8.3	-6.1	-8.6	-8.7	-9.7
AKTI	-8.7	-8.5	-7.9	-7.9	-8.1

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金缕半枫荷的水提取物抑制胰腺癌的作用机制：活性成分、关键靶点和信号通路

Therapeutic mechanism of aqueous extract of Semiliquidambar cathayensis Chang root for pancreatic cancer: the active components, therapeutic targets and pathways

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