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
• • 上一篇
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()
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:
Yan HUANG1(), Lulu QIN1, Shaoxing GUAN2, Yanping GUANG2, Yuru WEI2, Ailing CAO2, Dongmei LI3, Guining WEI3(), Qibiao SU1()
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:
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。
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.
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 |
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.
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 |
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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