基于分子动力学模拟探讨泽漆对淋巴结转移阳性胃癌的潜在干预作用

doi:10.5246/jcps.2025.07.048

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (7): 644-663.DOI: 10.5246/jcps.2025.07.048

基于分子动力学模拟探讨泽漆对淋巴结转移阳性胃癌的潜在干预作用

郑宜鋆¹^,², 王哲元¹^,², 王满才¹^,², 肖琪¹^,², 邓弘扬¹^,², 李戟玭¹^,², 张岭漪¹^,², 张有成¹^,²^,^*()

^1. 兰州大学第二临床医学院, 甘肃兰州 730030
^2. 兰州大学第二医院普通外科, 甘肃兰州 730030

收稿日期:2025-03-23 修回日期:2025-04-23 接受日期:2025-05-08 出版日期:2025-07-31 发布日期:2025-07-31
通讯作者: 张有成

Investigating the potential of Euphorbia helioscopia intervention in gastric cancer with positive lymph node metastasis: insights from molecular dynamics simulation

Yijun Zheng¹^,², Zheyuan Wang¹^,², Mancai Wang¹^,², Qi Xiao¹^,², Hongyang Deng¹^,², Jipin Li¹^,², Lingyi Zhang¹^,², Youcheng Zhang¹^,²^,^*()

¹ Lanzhou University Second Clinical Medical School, Lanzhou 730030, Gansu, China
² Lanzhou University Second Hospital Department of General Surgery, Lanzhou 730030, Gansu, China

Received:2025-03-23 Revised:2025-04-23 Accepted:2025-05-08 Online:2025-07-31 Published:2025-07-31
Contact: Youcheng Zhang
Supported by:
The Gansu Province University Industrial Support Plan (Grant No. 2023CYZC-05), the Cuiying Technology Innovation Project of Lanzhou University Second Hospital (Grant No. CY2022-MS-B04), the Doctoral Students Training Research Fund of Lanzhou University Second Hospital (Grant No. YJS-BD-32), and the Gansu Province Drug Regulatory Science Research Project in 2024(Grant No. 2024GSMPA032).

摘要/Abstract

摘要：

泽漆是一种天然植物, 因其抗肿瘤的特性而被广泛研究。然而, 对于淋巴结转移阳性的胃癌, 其治疗能力仍有待进一步研究。本研究旨在通过结合网络药理学、分子对接和分子动力学模拟的综合方法, 阐明泽漆在胃癌淋巴结转移治疗中的作用。首先, 确定并系统分析了泽漆与淋巴结转移阳性胃癌的共同靶点数据。随后进行分子对接, 验证主要成分与靶点之间的相互作用。最后, 采用分子动力学模拟, 通过MM-PBSA算法进行结合自由能的计算。结果表明, 在这种情况下, 泽漆主要的生物活性成分包括槲皮素和木犀草素, 靶向核心分子如EGFR和MMP9。其作用机制涉及的主要通路包括对EGFR酪氨酸激酶抑制剂的耐药性等。分子对接显示活性成分与关键靶点之间具有良好结合亲和力, 分子动力学和结合自由能分析显示木犀草素与MMP9之间具有稳定的相互作用。综上所述,在淋巴结转移阳性胃癌的治疗中, 泽漆具有多成分、多靶点、多途径的特点。该研究结果为其在肿瘤学中的潜在临床应用提供了有价值的理论依据。

关键词: 泽漆, 淋巴结转移, 胃癌, 分子动力学, 网络药理学, 分子对接

Abstract:

Euphorbia helioscopia, a natural plant recognized for its anti-tumor properties, has been extensively investigated in various cancers. However, its therapeutic potential in gastric cancer with positive lymph node metastasis remains underexplored. This study aimed to elucidate the role of E. helioscopia in treating gastric cancer with lymph node metastasis using an integrative approach that combined network pharmacology, molecular docking, and molecular dynamics simulations. Initially, shared target data between E. helioscopia and gastric cancer with positive lymph node metastasis were identified and systematically analyzed. Subsequently, molecular docking was conducted to validate the interactions between key components and targets. Finally, molecular dynamics simulations were employed, with binding free energy calculations performed using the MM-PBSA algorithm. The findings revealed that the primary bioactive compounds of E. helioscopia in this context included quercetin and luteolin, targeting core molecules such as EGFR and MMP9. Key pathways implicated in its mechanism of action included resistance to EGFR tyrosine kinase inhibitors, among others. Molecular docking demonstrated robust binding affinity between the active compounds and critical targets, with molecular dynamics and binding free energy analyses highlighting a particularly stable interaction between luteolin and MMP9. In conclusion, E. helioscopia exhibited a multi-component, multi-target, and multi-pathway therapeutic profile in treating gastric cancer with positive lymph node metastasis. These findings offered valuable theoretical insights supporting its potential clinical application in oncology.

Key words: Euphorbia helioscopia, Lymph node metastasis, Gastric cancer, Molecular dynamics, Network pharmacology, Molecular docking

Supporting:

郑宜鋆, 王哲元, 王满才, 肖琪, 邓弘扬, 李戟玭, 张岭漪, 张有成. 基于分子动力学模拟探讨泽漆对淋巴结转移阳性胃癌的潜在干预作用[J]. 中国药学(英文版), 2025, 34(7): 644-663.

Yijun Zheng, Zheyuan Wang, Mancai Wang, Qi Xiao, Hongyang Deng, Jipin Li, Lingyi Zhang, Youcheng Zhang. Investigating the potential of Euphorbia helioscopia intervention in gastric cancer with positive lymph node metastasis: insights from molecular dynamics simulation[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(7): 644-663.

图/表 13

Figure 1. Schematic diagram of research ideas.

Table 1. Bioactive components of E. helioscopia.

Table 2. Protein targets of gastric cancer-related diseases with positive lymph node metastasis obtained from the database.

Figure 2. Wayne diagram of the intersection target of E. helioscopia in treating gastric cancer with positive lymph node metastasis.

Figure 3. Core target network construction of E. helioscopia in the treatment of gastric cancer with positive lymph node metastasis.

Figure 4. Schematic diagram of PPI network of disease target, the key active ingredient of E. helioscopia in the treatment of gastric cancer with positive lymph node metastasis. (Note: blue is E. helioscopia, purple is compounds, red is the common target of E. helioscopia and gastric cancer with positive lymph node metastasis, and green is gastric cancer with positive lymph node metastasis. MOL000006 (luteolin), MOL000098 (quercetin), MOL000358 (beta-sitosterol), MOL000422 (kaempferol), MOL004328 (naringenin), MOL013425((2R)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxychroman-4-one).

Figure 5. Enrichment analysis of predicted target signaling pathways.

Figure 6. Enrichment analysis of predicted target gene function.

Table 3. Docking binding energy between key active components and core target molecules of E. helioscopia (kcal/mol).

Figure 7. Molecular docking mode of effective components of E. heliotropa-core target. Note: A: quercetin-EGFR; B: luteolin-EGFR; C: quercetin-MMP9; D: luteolin-MMP9; E: quercetin-BCL2; F: kaempferol-BCL2.

Figure 8. MD simulation results of quercetin-MMP9, luteolin-MMP9 and luteolin-EGFR. Note: hps is quercetin; mxcs is luteolin; A is Rg value; B is RMSD value; C is RMSF value; D is the H-bonds number; E is the SASA value.

Figure 9. Attribute and residue decomposition maps of quercetin-MMP9, luteolin-MMP9, and luteolin-EGFR. Note: A is quercetin-MMP9; B is luteolin-MMP9; C is luteolin-EGFR; VDWAALS: van der Waals energy; EEL; Electrostatic energy; EGB: Polar solvation energy; ESURF: Non-polar solvation energy; GGAS: Total gas phase free energy, VDWAALS + EEL; GSOLV: Total solvation free energy, EGB + ESURF; TOTAL = Total free energy, GSOLV + GGAS.

Table 4. Docked compounds MMPB/GBSA energy in kcal/mol.

参考文献 44

[1]	Zhu, H.Y.; Wu, J.; Zhang, Y.M.; Li, F.L.; Yang, J.; Qin, B.; Jiang, J.; Zhu, N.; Chen, M.Y.; Zou, B.C. Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection. World J. Gastroenterol. 2024, 30, 1990–2005.
[2]	Chen, K.; Zhang, J.; Ding, S.G. Research progress on lymph node micrometastasis in gastric cancer. Chin. J. Minimal. Invasive Surg. 2022, 05, 412–416.
[3]	Chen, W.Q.; Zheng, R.S.; Baade, P.D.; Zhang, S.W.; Zeng, H.M.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA A Cancer J. Clin. 2016, 66, 115–132.
[4]	Karpeh, M.S.; Leon, L.; Klimstra, D.; Brennan, M.F. Lymph node staging in gastric cancer: is location more important than number? an analysis of 1, 038 patients. Ann. Surg. 2000, 232, 362–371.
[5]	Brown, M.; Assen, F.P.; Leithner, A.; Abe, J.; Schachner, H.; Asfour, G.; Bago-Horvath, Z.; Stein, J.V.; Uhrin, P.; Sixt, M.; Kerjaschki, D. Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science. 2018, 359, 1408–1411.
[6]	Pereira, E.R.; Kedrin, D.; Seano, G.; Gautier, O.; Meijer, E.F.J.; Jones, D.; Chin, S.M.; Kitahara, S.; Bouta, E.M.; Chang, J.; Beech, E.; Jeong, H.S.; Carroll, M.C.; Taghian, A.G.; Padera, T.P. Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice. Science. 2018, 359, 1403–1407.
[7]	Zhang, W.; Guo, Y.W. Chemical studies on the constituents of the Chinese medicinal herb Euphorbia helioscopia L. Chem. Pharm. Bull. 2006, 54, 1037–1039.
[8]	Dou, D.; Qian, W. Exploring the mechanism of action of Euphorbia Helioscopia decoction in the treatment of non-small cell lung cancer based on network pharmacology and molecular docking technology. China Med. Pharm. 2023, 13, 47–50.
[9]	Gao, C.D. Exploring the intervention mechanism of Euphorbia Helioscopia decoction on lung adenocarcinoma based on PI3K/AKT signaling pathway. Jinan: Shandong Univ. Tradit. Chin. Med. 2022, 03, 104.
[10]	Shao, Y.; Liu, P.; Cheng, J.; Wang, M.; Wei, F.; Jiang, J.; Zhang, Y.; Reversal and mechanism of ethyl acetate extract of Euphorbia Helioscopia on SGC7901/DDP multidrug resistance. Chin. Tradit. Patent Med. 2017, 39, 1713–1717.
[11]	Mu, S.; Shang, S.; Yan, C.; Yang, F.; Hao, X.; Study on chemical components and antitumor activity of medicinal plant Euphorbia Helioscopia from Guizhou Province. J. Chin. Med. Mater. 2013, 36, 1092–1096.
[12]	Zhu, M.L.; Zhang, J.R.; Zhang, Q.R.; Lin, Y.; Li, X.Y.; Xu, W.; Xu, W. Integrated approach of network pharmacology and chemometrics for quality control of Chinese patent medicine: a case study on Huo-Luo-San. J. Chin. Pharm. Sci. 2024, 33, 819–836.
[13]	Filipe, H.A.L.; Loura, L.M.S. Molecular dynamics simulations: advances and applications. Mol. Basel Switz. 2022, 27, 2105.
[14]	Han, S.S.; Wang, Y. Elucidating the mechanisms underlying Taohong Siwu Decoction in preventing arteriovenous fistula failure: a comprehensive study combining network pharmacology, molecular docking, and dynamic simulation. J. Chin. Pharm. Sci. 2024, 33, 511–524.
[15]	Valdés-Tresanco, M.S.; Valdés-Tresanco, M.E.; Valiente, P.A.; Moreno, E. gmx_MMPBSA: a new tool to perform end-state free energy calculations with GROMACS. J. Chem. Theory Comput. 2021, 17, 6281–6291.
[16]	Qin, Y.; Wu, Y.; Ou, D.; Jiang, J. Study on chemical components of Euphorbia Helioscopia. Chin. Traditi. Herbal Drugs. 2018, 49, 1520–1524.
[17]	Wang, D.; Zhang, X.; Shao, Y.; Yu, H. Research progress on anti-tumor pharmacological effects and clinical applications of traditional Chinese medicine Euphorbia Helioscopia and its compound preparations. Tianjin J. Tradit. Chin. Med. 2023, 40, 402–408.
[18]	Wang, Yu.; Pen, T.; Long, S. Clinical efficacy observation of flavored Euphorbia Helioscopia decoction combined with NP regimen in the treatment of stage IV non-small cell lung cancer (NSCLC) of lung depression, phlegm stasis type. Taiyuan: Shanxi Univ. Chin. Med. 2020, 21, 39–41, 44.
[19]	Rong, Y.; Liu, S.H.; Tang, M.Z.; Yang, X.J. Quercetin inhibits the proliferative effect of gastric cancer cells by activating the pyroptosis pathway. Asian J. Surg. 2023, 46, 5286–5288.
[20]	Huang, Y.; Liao, Y.; Shen, Y.; Feng, Y. Quercetin enhances the induction activity of 5-fluorouracil on apoptosis of gastric cancer cells by inhibiting the expression level of c-Jun. Chin. J. Pathophysiol. 2018, 02, 206–211.
[21]	Rong, Y.; Liu, S.; Tang, M.; Cai, H. Study on the mechanism of quercetin activating the apoptosis pathway to inhibit the proliferation and migration of gastric cancer cells. Chin. J. Clin. Oncol. 2023, 20, 1033–1039.
[22]	Li, X.; Cheng, B.B.; Tan, J.L.; Wan, J.J.; Wang, Y.H.; Dai, A.G. Quercetin, the key constituent of Astragali Radix, modulates ferroptosis in PASMCs and attenuates hypoxia pulmonary hypertension via the MAPK signaling pathway. J. Chin. Pharm. Sci. 2024, 33, 714–729.
[23]	Chi, Z.; Zhang, H.; Cai, Y.; Xu, Z. Quercetin inhibits the migration of oxaliplatin resistant gastric cancer cells through the PI3K/AKT signaling pathway. Pract. Pharm. Clin. Remed. 2024, 27(02), 81–85.
[24]	Liu, W.; Wang, Y.; Li, J.; Du, G. The effect of quercetin on postoperative tumor metastasis in mice. J. Henan Univ. (Med. Sci.). 2013, 02, 93–96.
[25]	Xie, J.; Duan, Z.; Liu, X. Research progress on the anti-tumor effect of luteolin. Anti-Tumor Pharm. 2024, 02, 173–178.
[26]	Song, S.Y.; Su, Z.L.; Xu, H.; Niu, M.Y.; Chen, X.F.; Min, H.Y.; Zhang, B.; Sun, G.B.; Xie, S.J.; Wang, H.W.; Gao, Q. Luteolin selectively kills STAT3 highly activated gastric cancer cells through enhancing the binding of STAT3 to SHP-1. Cell Death Dis. 2017, 8, e2612.
[27]	Guo, Y.; Chen, Y.; Wang, L.; Xing, H.; Hu, S. Study on the anti proliferative and anti migratory effects of magnolol on gastric cancer cells through HIF-1α. Chin. Pharm. J. 2021, 16, 1313–1319.
[28]	Shin, E.J.; Choi, H.K.; Sung, M.J.; Park, J.H.; Chung, M.Y.; Chung, S.; Hwang, J.T. Anti-tumour effects of beta-sitosterol are mediated by AMPK/PTEN/HSP90 axis in AGS human gastric adenocarcinoma cells and xenograft mouse models. Biochem. Pharmacol. 2018, 152, 60–70.
[29]	Wang, J.; Liu, J.; Chen, F.; Zhou, Z.; Chen, Y.; Li, Y.; Luo, X.; Luo, G.; Yang, Y.; Zhu, B. Study on the effect of β-sitosterol on human costimulatory cells killing gastric cancer SGC-7901 cells and its mechanism. Immunological. J. 2014, 07, 578–584.
[30]	Niu, S.; Gong, H.; Fu, X.; Su, Y. Research progress of IL-17 and its mediated signaling pathway in gastric cancer. J. Med. Postgraduates. 2022, 06, 660–663.
[31]	Cheng, T.C.; Din, Z.H.; Su, J.H.; Wu, Y.J.; Liu, C.I. Sinulariolide suppresses cell migration and invasion by inhibiting matrix metalloproteinase-2/-9 and urokinase through the PI3K/AKT/mTOR signaling pathway in human bladder cancer cells. Mar. Drugs. 2017, 15, 238.
[32]	Wang, Y.D.; Wu, H.; Wu, X.L.; Bian, Z.Q.; Gao, Q. Interleukin 17A promotes gastric cancer invasiveness via NF-κB mediated matrix metalloproteinases 2 and 9 expression. PLoS One. 2014, 9, e96678.
[33]	Zuo, E.D.; Lu, Y.; Yan, M.; Pan, X.T.; Cheng, X. Increased expression of hepcidin and associated upregulation of JAK/STAT3 signaling in human gastric cancer. Oncol. Lett. 2018, 15, 2236–2244.
[34]	Deng, J.; Liang, H.; Sun, D.; Pan, Y.; Wu, L.; Xu, Y.; Dong, Q.; Hou, Y.; Xie, X.; Guo, X. Study on the mechanism of downregulation of JAK/STAT3 signaling pathway activity by RNF180 and inhibition of lymph node metastasis in gastric cancer. Tianjin: Tianjin Med. Univ. Cancer Inst. Hospital. 2020.
[35]	Zhong, W.; Li, Q.; Li, K.; Xu, X.; Wei, Y.; Zhu, Y.; Zhu, Z. Upregulation of IL-17A levels by human bone marrow-derived mesenchymal stem cells in the tumor microenvironment activates the PI3K/Akt pathway to promote the growth and chemotherapy resistance of diffuse large B-cell lymphoma. China Cancer. 2020, 05, 379–390.
[36]	Feng, M.J.; Wang, Y.D.; Chen, K.L.; Bian, Z.Q.; Wu, J.F.; Gao, Q. IL-17A promotes the migration and invasiveness of cervical cancer cells by coordinately activating MMPs expression via the p38/NF-κB signal pathway. PLoS One. 2014, 9, e108502.
[37]	Amatya, N.; Garg, A.V.; Gaffen, S.L. IL-17 signaling: the Yin and the Yang. Trends Immunol. 2017, 38, 310–322.
[38]	Bhayal, A.C.; Krishnaveni, D.; RangaRao, K.P.; Bogadi, V.; Suman, C.; Jyothy, A.; Nallari, P.; Venkateshwari, A. Role of tumor necrosis factor-α-308 G/A promoter polymorphism in gastric cancer. Saudi J. Gastroenterol. 2013, 19, 0.
[39]	Ni, X.; Zhang, Z.; Wu, J. Expression of HIF-1α protein in gastric cancer and its relationship with Wnt signaling pathway and epithelial mesenchymal transition. Chin. J. Clin. Exper. Pathol. 2014, 02, 140–144.
[40]	Jing, Y.; Bai, X.; Li, W. The effect and mechanism of Lizard Stomach Health Formula on gastric cancer liver metastasis based on HIF-1α-mediated PI3K/AKT signaling pathway. Chin. J. Gerontol. 2023, 12, 2943–2947.
[41]	Li, F.; Liu, B.H.; Gao, Y.; Liu, Y.L.; Xu, Y.; Tong, W.D.; Zhang, A.P. Upregulation of microRNA-107 induces proliferation in human gastric cancer cells by targeting the transcription factor FOXO1. FEBS Lett. 2014, 588, 538–544.
[42]	Park, J.; Ko, Y.S.; Yoon, J.; Kim, M.A.; Park, J.W.; Kim, W.H.; Choi, Y.; Kim, J.H.; Cheon, Y.; Lee, B.L. The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway. Gastric Cancer. 2014, 17, 423–430.
[43]	Wu, X.D.; Xu, L.Y.; Li, E.M.; Dong, G. Application of molecular dynamics simulation in biomedicine. Chem. Biol. Drug Des. 2022, 99, 789–800.
[44]	Lu, C.L.; Peng, X.; Lu, D.N. Molecular dynamics simulation of protein cages. Methods Mol. Biol. 2023, 2671, 273–305.

基于分子动力学模拟探讨泽漆对淋巴结转移阳性胃癌的潜在干预作用

Investigating the potential of Euphorbia helioscopia intervention in gastric cancer with positive lymph node metastasis: insights from molecular dynamics simulation

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