Machine Learning Algorithms Identify Target Genes and the Molecular Mechanism of Matrine against Diffuse Large B-cell Lymphoma
- Autores: Zhu Y.1, Ning Z.2, Li X.2, Lin Z.3
-
Afiliações:
- Department of Traditional Chinese Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine,
- Department of Cardiology, Shanghai Pudong New District Zhoupu Hospital, Shanghai University of Medicine & Health Sciences,
- onghua Hospital, Shanghai University of Traditional Chinese Medicine
- Edição: Volume 20, Nº 6 (2024)
- Páginas: 847-859
- Seção: Chemistry
- URL: https://rjpbr.com/1573-4099/article/view/644368
- DOI: https://doi.org/10.2174/1573409920666230821102806
- ID: 644368
Citar
Texto integral
Resumo
Background:Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide. Novel treatment strategies are still needed for this disease.
Objective:The present study aimed to systematically explore the potential targets and molecular mechanisms of matrine in the treatment of DLBCL.
Methods:Potential matrine targets were collected from multiple platforms. Microarray data and clinical characteristics of DLBCL were downloaded from publicly available database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to identify the hub genes of DLBCL using R software. Then, the shared target genes between matrine and DLBCL were identified as the potential targets of matrine against DLBCL. The least absolute shrinkage and selection operator (LASSO) algorithm was used to determine the final core target genes, which were further verified by molecular docking simulation and receiver operating characteristic (ROC) curve analysis. Functional analysis was also performed to elucidate the potential mechanisms.
Results:A total of 222 matrine target genes and 1269 DLBCL hub genes were obtained through multiple databases and machine learning algorithms. From the nine shared target genes of matrine and DLBCL, five final core target genes, including CTSL, NR1H2, PDPK1, MDM2, and JAK3, were identified. Molecular docking showed that the binding of matrine to the core genes was stable. ROC curves also suggested close associations between the core genes and DLBCL. Additionally, functional analysis showed that the therapeutic effect of matrine against DLBCL may be related to the PI3K-Akt signaling pathway.
Conclusion:Matrine may target five genes and the PI3K-Akt signaling pathway in DLBCL treatment.
Palavras-chave
Sobre autores
Yidong Zhu
Department of Traditional Chinese Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine,
Email: info@benthamscience.net
Zhongping Ning
Department of Cardiology, Shanghai Pudong New District Zhoupu Hospital, Shanghai University of Medicine & Health Sciences,
Email: info@benthamscience.net
Ximing Li
Department of Cardiology, Shanghai Pudong New District Zhoupu Hospital, Shanghai University of Medicine & Health Sciences,
Autor responsável pela correspondência
Email: info@benthamscience.net
Zhikang Lin
onghua Hospital, Shanghai University of Traditional Chinese Medicine
Autor responsável pela correspondência
Email: info@benthamscience.net
Bibliografia
- Sehn, L.H.; Salles, G. Diffuse large B-Cell lymphoma. N. Engl. J. Med., 2021, 384(9), 842-858. doi: 10.1056/NEJMra2027612 PMID: 33657296
- Susanibar-Adaniya, S.; Barta, S.K. 2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management. Am. J. Hematol., 2021, 96(5), 617-629. doi: 10.1002/ajh.26151 PMID: 33661537
- Cheson, B.D.; Nowakowski, G.; Salles, G. Diffuse large B-cell lymphoma: New targets and novel therapies. Blood Cancer J., 2021, 11(4), 68. doi: 10.1038/s41408-021-00456-w PMID: 33820908
- Spinner, M.A.; Advani, R.H. Current frontline treatment of diffuse large B-Cell lymphoma. Oncology, 2022, 36(1), 51-58. PMID: 35089671
- He, M.Y.; Kridel, R. Treatment resistance in diffuse large B-cell lymphoma. Leukemia, 2021, 35(8), 2151-2165. doi: 10.1038/s41375-021-01285-3 PMID: 34017074
- Crump, M.; Neelapu, S.S.; Farooq, U.; Van Den Neste, E.; Kuruvilla, J.; Westin, J.; Link, B.K.; Hay, A.; Cerhan, J.R.; Zhu, L.; Boussetta, S.; Feng, L.; Maurer, M.J.; Navale, L.; Wiezorek, J.; Go, W.Y.; Gisselbrecht, C. Outcomes in refractory diffuse large B-cell lymphoma: Results from the international SCHOLAR-1 study. Blood, 2017, 130(16), 1800-1808. doi: 10.1182/blood-2017-03-769620 PMID: 28774879
- Sun, Y.; Xu, L.; Cai, Q.; Wang, M.; Wang, X.; Wang, S.; Ni, Z. Research progress on the pharmacological effects of matrine. Front. Neurosci., 2022, 16, 977374. doi: 10.3389/fnins.2022.977374 PMID: 36110092
- Sun, X.Y.; Jia, L.Y.; Rong, Z.; Zhou, X.; Cao, L.Q.; Li, A.H.; Guo, M.; Jin, J.; Wang, Y.D.; Huang, L.; Li, Y.H.; He, Z.J.; Li, L.; Ma, R.K.; Lv, Y.F.; Shao, K.K.; Zhang, J.; Cao, H.L. Research advances on matrine. Front Chem., 2022, 10, 867318. doi: 10.3389/fchem.2022.867318 PMID: 35433636
- Chen, F.; Pan, Y.; Xu, J.; Liu, B.; Song, H. Research progress of matrines anticancer activity and its molecular mechanism. J. Ethnopharmacol., 2022, 286, 114914. doi: 10.1016/j.jep.2021.114914 PMID: 34919987
- Li, X.; Tang, Z.; Wen, L.; Jiang, C.; Feng, Q. Matrine: A review of its pharmacology, pharmacokinetics, toxicity, clinical application and preparation researches. J. Ethnopharmacol., 2021, 269, 113682. doi: 10.1016/j.jep.2020.113682 PMID: 33307055
- Zhang, H.; Chen, L.; Sun, X.; Yang, Q.; Wan, L.; Guo, C. Matrine: A promising natural product with various pharmacological activities. Front. Pharmacol., 2020, 11, 588. doi: 10.3389/fphar.2020.00588 PMID: 32477114
- Gu, J.; Zhang, Y.; Wang, X.; Xiang, J.; Deng, S.; Wu, D.; Chen, J.; Yu, L.; Zhou, Y.; Wang, Y.; Shen, J. Matrine inhibits the growth of natural killer/T-cell lymphoma cells by modulating CaMKIIγ-c-Myc signaling pathway. BMC Complement. Med. Ther., 2020, 20(1), 214. doi: 10.1186/s12906-020-03006-2 PMID: 32641029
- Yixiang, H.; Shenghui, Z.; Jianbo, W.; Kang, Y.; Yu, Z.; Lihui, Y.; Laixi, B. Matrine induces apoptosis of human multiple myeloma cells via activation of the mitochondrial pathway. Leuk. Lymphoma, 2010, 51(7), 1337-1346. doi: 10.3109/10428194.2010.488708 PMID: 20528251
- Wu, D.; Shao, K.; Zhou, Q.; Sun, J.; Wang, Z.; Yan, F.; Liu, T.; Wu, X.; Ye, B.; Huang, H. Autophagy and ubiquitin-mediated proteolytic degradation of PML/Rarα fusion protein in matrine-induced differentiation sensitivity recovery of ATRA-resistant APL (NB4-LR1) cells: In vitro and in vivo studies. Cell. Physiol. Biochem., 2018.
- Ma, L.; Zhu, Z.; Jiang, L.; Sun, X.; Lu, X.; Zhou, M.; Qian, S.; Jianyong, L. Matrine suppresses cell growth of human chronic myeloid leukemia cells via its inhibition of the interleukin-6/Janus activated kinase/signal transducer and activator of transcription 3 signaling cohort. Leuk. Lymphoma, 2015, 56(10), 2923-2930. doi: 10.3109/10428194.2015.1007507 PMID: 25629992
- Gu, J.; Wang, X.; Zhang, L.; Xiang, J.; Li, J.; Chen, Z.; Zhang, Y.; Chen, J.; Shen, J. Matrine suppresses cell growth of diffuse large B-cell lymphoma via inhibiting CaMKIIγ/c-Myc/CDK6 signaling pathway. BMC Complement. Med. Ther., 2021, 21(1), 163. doi: 10.1186/s12906-021-03315-0 PMID: 34088288
- Greener, J.G.; Kandathil, S.M.; Moffat, L.; Jones, D.T. A guide to machine learning for biologists. Nat. Rev. Mol. Cell Biol., 2022, 23(1), 40-55. doi: 10.1038/s41580-021-00407-0 PMID: 34518686
- Yu, J.L.; Dai, Q.Q.; Li, G.B. Deep learning in target prediction and drug repositioning: Recent advances and challenges. Drug Discov. Today, 2022, 27(7), 1796-1814. doi: 10.1016/j.drudis.2021.10.010 PMID: 34718208
- Song, T.; Zhang, X.; Ding, M.; Rodriguez-Paton, A.; Wang, S.; Wang, G. DeepFusion: A deep learning based multi-scale feature fusion method for predicting drug-target interactions. Methods, 2022, 204, 269-277. doi: 10.1016/j.ymeth.2022.02.007 PMID: 35219861
- Thafar, M.A.; Alshahrani, M.; Albaradei, S.; Gojobori, T.; Essack, M.; Gao, X. Affinity2Vec: Drug-target binding affinity prediction through representation learning, graph mining, and machine learning. Sci. Rep., 2022, 12(1), 4751. doi: 10.1038/s41598-022-08787-9 PMID: 35306525
- Langfelder, P.; Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics, 2008, 9(1), 559. doi: 10.1186/1471-2105-9-559 PMID: 19114008
- Zhang, B; Horvath, S A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol, 2005, 4, Article17. doi: 10.2202/1544-6115.1128
- Wu, C.; Huang, Z.H.; Meng, Z.Q.; Fan, X.T.; Lu, S.; Tan, Y.Y.; You, L.M.; Huang, J.Q.; Stalin, A.; Ye, P.Z.; Wu, Z.S.; Zhang, J.Y.; Liu, X.K.; Zhou, W.; Zhang, X.M.; Wu, J.R. A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation. Chin. Med., 2021, 16(1), 121. doi: 10.1186/s13020-021-00534-y PMID: 34809653
- Girnita, L.; Girnita, A.; Larsson, O. Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor. Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8247-8252. doi: 10.1073/pnas.1431613100 PMID: 12821780
- Li, M.; Brooks, C.L.; Kon, N.; Gu, W. A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol. Cell, 2004, 13(6), 879-886. doi: 10.1016/S1097-2765(04)00157-1 PMID: 15053880
- Sun, C.; Li, M.; Zhang, L.; Sun, F.; Chen, H.; Xu, Y.; Lan, Y.; Zhang, L.; Lu, S.; Zhu, J.; Huang, J.; Wang, J.; Hu, Y.; Feng, Y.; Zhang, Y. IDO1 plays a tumor-promoting role via MDM2-mediated suppression of the p53 pathway in diffuse large B-cell lymphoma. Cell Death Dis., 2022, 13(6), 572. doi: 10.1038/s41419-022-05021-2 PMID: 35760783
- Sun, C.; Li, M.; Feng, Y.; Sun, F.; Zhang, L.; Xu, Y.; Lu, S.; Zhu, J.; Huang, J.; Wang, J.; Hu, Y.; Zhang, Y. MDM2-P53 signaling pathway-mediated upregulation of CDC20 promotes progression of human diffuse large B-cell lymphoma. OncoTargets Ther., 2020, 13, 10475-10487. doi: 10.2147/OTT.S253758 PMID: 33116627
- Lu, T.X.; Young, K.H.; Xu, W.; Li, J.Y. TP53 dysfunction in diffuse large B-cell lymphoma. Crit. Rev. Oncol. Hematol., 2016, 97, 47-55. doi: 10.1016/j.critrevonc.2015.08.006 PMID: 26315382
- Wang, P.; Lushnikova, T.; Odvody, J.; Greiner, T.C.; Jones, S.N.; Eischen, C.M. Elevated Mdm2 expression induces chromosomal instability and confers a survival and growth advantage to B cells. Oncogene, 2008, 27(11), 1590-1598. doi: 10.1038/sj.onc.1210788 PMID: 17828300
- Møller, M.B.; Ino, Y.; Gerdes, A-M.; Skøjdt, K.; Louis, D.N.; Pedersen, N.T. Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma. Leukemia, 1999, 13(3), 453-459. doi: 10.1038/sj.leu.2401315 PMID: 10086736
- Luo, Q.; Pan, W.; Zhou, S.; Wang, G.; Yi, H.; Zhang, L.; Yan, X.; Yuan, L.; Liu, Z.; Wang, J.; Chen, H.; Qiu, M.; Yang, D.; Sun, J. A novel BCL-2 inhibitor APG-2575 exerts synthetic lethality with BTK or MDM2-p53 inhibitor in diffuse large B-cell lymphoma. Oncol. Res., 2020, 28(4), 331-344. doi: 10.3727/096504020X15825405463920 PMID: 32093809
- Drakos, E.; Singh, R.R.; Rassidakis, G.Z.; Schlette, E.; Li, J.; Claret, F.X.; Ford, R.J., Jr; Vega, F.; Medeiros, L.J. Activation of the p53 pathway by the MDM2 inhibitor nutlin-3a overcomes BCL2 overexpression in a preclinical model of diffuse large B-cell lymphoma associated with t(14;18)(q32;q21). Leukemia, 2011, 25(5), 856-867. doi: 10.1038/leu.2011.28 PMID: 21394100
- Luo, B.; Gu, Y.; Wang, X.; Chen, G.; Peng, Z. Identification of potential drugs for diffuse large b-cell lymphoma based on bioinformatics and connectivity map database. Pathol. Res. Pract., 2018, 214(11), 1854-1867. doi: 10.1016/j.prp.2018.09.013 PMID: 30244948
- Simoncic, P.D.; Lee-Loy, A.; Barber, D.L.; Tremblay, M.L.; McGlade, C.J. The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr. Biol., 2002, 12(6), 446-453. doi: 10.1016/S0960-9822(02)00697-8 PMID: 11909529
- Sharfe, N.; Dadi, H.K.; Roifman, C.M. JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3′ kinase. Blood, 1995, 86(6), 2077-2085. doi: 10.1182/blood.V86.6.2077.bloodjournal8662077 PMID: 7662955
- Johnston, J.A.; Kawamura, M.; Kirken, R.A.; Chen, Y.Q.; Blake, T.B.; Shibuya, K.; Ortaldo, J.R.; McVicar, D.W.; OShea, J.J. Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. Nature, 1994, 370(6485), 151-153. doi: 10.1038/370151a0 PMID: 8022485
- Scheid, M.P.; Marignani, P.A.; Woodgett, J.R. Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B. Mol. Cell. Biol., 2002, 22(17), 6247-6260. doi: 10.1128/MCB.22.17.6247-6260.2002 PMID: 12167717
- King, C.C.; Gardiner, E.M.M.; Zenke, F.T.; Bohl, B.P.; Newton, A.C.; Hemmings, B.A.; Bokoch, G.M. p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1). J. Biol. Chem., 2000, 275(52), 41201-41209. doi: 10.1074/jbc.M006553200 PMID: 10995762
- Jensen, C.J.; Buch, M.B.; Krag, T.O.; Hemmings, B.A.; Gammeltoft, S.; Frödin, M. 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J. Biol. Chem., 1999, 274(38), 27168-27176. doi: 10.1074/jbc.274.38.27168 PMID: 10480933
- Sakurabashi, A.; Wada-Hiraike, O.; Hirano, M.; Fu, H.; Isono, W.; Fukuda, T.; Morita, Y.; Tanikawa, M.; Miyamoto, Y.; Oda, K.; Kawana, K.; Osuga, Y.; Fujii, T. CCAR2 negatively regulates nuclear receptor LXRα by competing with SIRT1 deacetylase. J. Steroid Biochem. Mol. Biol., 2015, 149, 80-88. doi: 10.1016/j.jsbmb.2015.02.001 PMID: 25661920
- Cao, Y.; Liu, X.; Li, Y.; Lu, Y.; Zhong, H.; Jiang, W.; Chen, A.F.; Billiar, T.R.; Yuan, H.; Cai, J. Cathepsin L activity correlates with proteinuria in chronic kidney disease in humans. Int. Urol. Nephrol., 2017, 49(8), 1409-1417. doi: 10.1007/s11255-017-1626-7 PMID: 28534128
- Liu, C.L.; Guo, J.; Zhang, X.; Sukhova, G.K.; Libby, P.; Shi, G.P. Cysteine protease cathepsins in cardiovascular disease: From basic research to clinical trials. Nat. Rev. Cardiol., 2018, 15(6), 351-370. doi: 10.1038/s41569-018-0002-3 PMID: 29679024
- Xu-Monette, Z.Y.; Møller, M.B.; Tzankov, A.; Montes-Moreno, S.; Hu, W.; Manyam, G.C.; Kristensen, L.; Fan, L.; Visco, C.; Dybkær, K.; Chiu, A.; Tam, W.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.L.; van Krieken, J.H.; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.M.; Wu, L.; Zhao, X.; Bueso-Ramos, C.E.; Wang, S.A.; Go, R.S.; Li, Y.; Winter, J.N.; Piris, M.A.; Medeiros, L.J.; Young, K.H. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: A report from the International DLBCL Rituximab-CHOP Consortium Program. Blood, 2013, 122(15), 2630-2640. doi: 10.1182/blood-2012-12-473702 PMID: 23982177
- Dlouhy, I.; Karube, K.; Enjuanes, A.; Salaverria, I.; Nadeu, F.; Ramis-Zaldivar, J.E.; Valero, J.G.; Rivas-Delgado, A.; Magnano, L.; Martin-García, D.; Pérez-Galán, P.; Clot, G.; Rovira, J.; Jares, P.; Balagué, O.; Giné, E.; Mozas, P.; Briones, J.; Sancho, J.M.; Salar, A.; Mercadal, S.; Alcoceba, M.; Valera, A.; Campo, E.; López-Guillermo, A. Revised International Prognostic Index and genetic alterations are associated with early failure to R‐CHOP in patients with diffuse large B‐cell lymphoma. Br. J. Haematol., 2022, 196(3), 589-598. doi: 10.1111/bjh.17858 PMID: 34632572
- Hedström, G.; Thunberg, U.; Amini, R.M.; Zainuddin, N.; Enblad, G.; Berglund, M. The MDM2 polymorphism SNP309 is associated with clinical characteristics and outcome in diffuse large B-cell lymphoma. Eur. J. Haematol., 2014, 93(6), 500-508. doi: 10.1111/ejh.12388 PMID: 24889555
- Todorovic Balint, M.; Jelicic, J.; Mihaljevic, B.; Kostic, J.; Stanic, B.; Balint, B.; Pejanovic, N.; Lucic, B.; Tosic, N.; Marjanovic, I.; Stojiljkovic, M.; Karan-Djurasevic, T.; Perisic, O.; Rakocevic, G.; Popovic, M.; Raicevic, S.; Bila, J.; Antic, D.; Andjelic, B.; Pavlovic, S. Gene mutation profiles in primary diffuse large B cell lymphoma of central nervous system: Next generation sequencing analyses. Int. J. Mol. Sci., 2016, 17(5), 683. doi: 10.3390/ijms17050683 PMID: 27164089
- Feng, Y.; Lin, J.; Liu, Y.; Tang, Y.; Zhou, Y.; Zhong, M. Investigation of expressions of PDK 1, PLK 1 and c‐Myc in diffuse large B‐cell lymphoma. Int. J. Exp. Pathol., 2019, 100(1), 32-40. doi: 10.1111/iep.12307 PMID: 30912195
- Porta, C.; Paglino, C.; Mosca, A. Targeting PI3K/Akt/mTOR signaling in cancer. Front. Oncol., 2014, 4, 64. doi: 10.3389/fonc.2014.00064 PMID: 24782981
- Alzahrani, A.S. PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside. Semin. Cancer Biol., 2019, 59, 125-132. doi: 10.1016/j.semcancer.2019.07.009 PMID: 31323288
- Sun, F.; Fang, X.; Wang, X. Signal pathways and therapeutic prospects of diffuse large B cell lymphoma. Anticancer. Agents Med. Chem., 2020, 19(17), 2047-2059. doi: 10.2174/1871520619666190925143216 PMID: 32009599
- Xu, W.; Berning, P.; Lenz, G. Targeting B-cell receptor and PI3K signaling in diffuse large B-cell lymphoma. Blood, 2021, 138(13), 1110-1119. doi: 10.1182/blood.2020006784 PMID: 34320160
- Majchrzak, A.; Witkowska, M.; Smolewski, P. Inhibition of the PI3K/Akt/mTOR signaling pathway in diffuse large B-cell lymphoma: Current knowledge and clinical significance. Molecules, 2014, 19(9), 14304-14315. doi: 10.3390/molecules190914304 PMID: 25215588
- Pfeifer, M.; Lenz, G. PI3K/AKT addiction in subsets of diffuse large B-cell lymphoma. Cell Cycle, 2013, 12(21), 3347-3348. doi: 10.4161/cc.26575 PMID: 24091535
- Wang, L.; Li, L.; Young, K.H. New agents and regimens for diffuse large B cell lymphoma. J. Hematol. Oncol., 2020, 13(1), 175. doi: 10.1186/s13045-020-01011-z PMID: 33317571
- Lenz, G.; Hawkes, E.; Verhoef, G.; Haioun, C.; Thye Lim, S.; Seog Heo, D.; Ardeshna, K.; Chong, G.; Haaber, J.; Shi, W.; Gorbatchevsky, I.; Lippert, S.; Hiemeyer, F.; Piraino, P.; Beckmann, G.; Peña, C.; Buvaylo, V.; Childs, B.H.; Salles, G. Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma. Leukemia, 2020, 34(8), 2184-2197. doi: 10.1038/s41375-020-0743-y PMID: 32060403
- Coleman, M.; Belada, D.; Casasnovas, R.O.; Gressin, R.; Lee, H.P.; Mehta, A.; Munoz, J.; Verhoef, G.; Corrado, C.; DeMarini, D.J.; Zhao, W.; Li, J.; Fay, K. Phase 2 study of parsaclisib (INCB050465), a highly selective, next-generation PI3Kδ inhibitor, in relapsed or refractory diffuse large B-cell lymphoma (CITADEL-202). Leuk. Lymphoma, 2021, 62(2), 368-376. doi: 10.1080/10428194.2020.1832660 PMID: 33140664
- Li, Q.; Huang, H.; He, Z.; Sun, Y.; Tang, Y.; Shang, X.; Wang, C. Regulatory effects of antitumor agent matrine on FOXO and PI3K-AKT pathway in castration-resistant prostate cancer cells. Sci. China Life Sci., 2018, 61(5), 550-558. doi: 10.1007/s11427-016-9050-6 PMID: 29119376
- Yang, Y.; Guo, J.X.; Shao, Z.Q.; Gao, J.P. Matrine inhibits bladder cancer cell growth and invasion in vitro through PI3K/AKT signaling pathway: An experimental study. Asian Pac. J. Trop. Med., 2017, 10(5), 515-519. doi: 10.1016/j.apjtm.2017.05.009 PMID: 28647190
- Peng, X.; Zhou, D.; Wang, X.; Hu, Z.; Yan, Y.; Huang, J. Matrine suppresses proliferation and invasion of SGC7901 cells through inactivation of PI3K/Akt/uPA pathway. Ann. Clin. Lab. Sci., 2016, 46(5), 457-462. PMID: 27650610
- Wan, Q.; Du, Z.; Fang, Z.; Cheng, H.; Li, C.; Zhou, X. Matrine induces apoptosis and autophagy in human lung adenocarcinoma cells via upregulation of Cavin3 and suppression of PI3K/AKT pathway. J. BUON, 2020, 25(3), 1512-1516. PMID: 32862598
- Kupcova, K.; Senavova, J.; Herman, V.; Chrbolkova, T.; Ondeckova, I.; Pacheco-Blanco, M.; Havranek, O. Combinatorial PI3K/AKT pathway inhibition as a therapeutic approach in diffuse large B-Cell lymphoma. Blood, 2022, 140(Suppl. 1), 3149-3150. doi: 10.1182/blood-2022-166121
- Charwudzi, A.; Meng, Y.; Hu, L.; Ding, C.; Pu, L.; Li, Q.; Xu, M.; Zhai, Z.; Xiong, S. Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma. PeerJ, 2021, 9, e12394. doi: 10.7717/peerj.12394 PMID: 34760386
Arquivos suplementares
