The Role of Emodin in the Treatment of Bladder Cancer Based on Network Pharmacology and Experimental Verification
- Authors: Liu F.1, Li J.1, Zhou B.1, Shen Y.2, Tang J.3, Han J.3, Chen C.3, Shao K.1, Chen H.4, Yuan L.3
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Affiliations:
- The First Clinical Medical College, Nanjing University of Chinese Medicine
- Department of Urology,, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Second Chinese Medicine Hospital
- Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine
- The First Clinical Medical College,, Nanjing University of Chinese Medicine
- Issue: Vol 27, No 11 (2024)
- Pages: 1661-1675
- Section: Chemistry
- URL: https://vietnamjournal.ru/1386-2073/article/view/643920
- DOI: https://doi.org/10.2174/0113862073294990240122140121
- ID: 643920
Cite item
Full Text
Abstract
Background and Purpose:Emodin, a compound derived from rhubarb and various traditional Chinese medicines, exhibits a range of pharmacological actions, including antiinflammatory, antiviral, and anticancer properties. Nevertheless, its pharmacological impact on bladder cancer (BLCA) and the underlying mechanism are still unclear. This research aimed to analyze the pharmacological mechanisms of Emodin against BLCA using network pharmacology analysis and experimental verification.
Methods::Initially, network pharmacology was employed to identify core targets and associated pathways affected by Emodin in bladder cancer. Subsequently, the expression of key targets in normal bladder tissues and BLCA tissues was assessed by searching the GEPIA and HPA databases. The binding energy between Emodin and key targets was predicted using molecular docking. Furthermore, in vitro experiments were carried out to confirm the predictions made with network pharmacology.
Results::Our analysis identified 148 common genes targeted by Emodin and BLCA, with the top ten target genes including TP53, HSP90AA1, EGFR, MYC, CASP3, CDK1, PTPN11, EGF, ESR1, and TNF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated a significant correlation between Emodin and the PI3KAKT pathway in the context of BLCA. Molecular docking investigations revealed a strong affinity between Emodin and critical target proteins. In vitro experiments demonstrated that Emodin inhibits T24 proliferation, migration, and invasion while inducing cell apoptosis. The findings also indicated that Emodin reduces both PI3K and AKT protein and mRNA expression, suggesting that Emodin may mitigate BLCA by modulating the PI3K-AKT signaling pathway.
Conclusion::This study integrates network pharmacology with in vitro experimentation to elucidate the potential mechanisms underlying the action of Emodin against BLCA. The results of this research enhance our understanding of the pharmacological mechanisms by which Emodin may be employed in treating BLCA.
About the authors
Fule Liu
The First Clinical Medical College, Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Jianghao Li
The First Clinical Medical College, Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Boruo Zhou
The First Clinical Medical College, Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Yang Shen
Department of Urology,, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Second Chinese Medicine Hospital
Email: info@benthamscience.net
Jingyuan Tang
Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Jie Han
Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Changpeng Chen
Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Kang Shao
The First Clinical Medical College, Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Haojie Chen
The First Clinical Medical College,, Nanjing University of Chinese Medicine
Email: info@benthamscience.net
Lin Yuan
Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine
Author for correspondence.
Email: info@benthamscience.net
References
- Frick, C.; Rumgay, H.; Vignat, J.; Ginsburg, O.; Nolte, E.; Bray, F.; Soerjomataram, I. Quantitative estimates of preventable and treatable deaths from 36 cancers worldwide: A population-based study. Lancet Glob. Health, 2023, 11(11), e1700-e1712. doi: 10.1016/S2214-109X(23)00406-0 PMID: 37774721
- Zhang, H.; Zhou, C.; Zhang, Z.; Yao, S.; Bian, Y.; Fu, F.; Luo, H.; Li, Y.; Yan, S.; Ge, Y.; Chen, Y.; Zhan, K.; Yue, M.; Du, W.; Tian, K.; Jin, H.; Li, X.; Tong, P.; Ruan, H.; Wu, C. Integration of network pharmacology and experimental validation to explore the pharmacological mechanisms of zhuanggu busui formula against osteoporosis. Front. Endocrinol., 2022, 12, 841668. doi: 10.3389/fendo.2021.841668 PMID: 35154014
- Dong, X.; Zeng, Y.; Liu, Y.; You, L.; Yin, X.; Fu, J.; Ni, J. Aloe-emodin: A review of its pharmacology, toxicity, and pharmacokinetics. Phytother. Res., 2020, 34(2), 270-281. doi: 10.1002/ptr.6532 PMID: 31680350
- Chen, S.; Zhang, Z.; Zhang, J. Emodin enhances antitumor effect of paclitaxel on human non-small-cell lung cancer cells in vitro and in vivo. Drug Des. Devel. Ther., 2019, 13, 1145-1153. doi: 10.2147/DDDT.S196319 PMID: 31114158
- Dai, G.; Ding, K.; Cao, Q.; Xu, T.; He, F.; Liu, S.; Ju, W. Emodin suppresses growth and invasion of colorectal cancer cells by inhibiting VEGFR2. Eur. J. Pharmacol., 2019, 859, 172525. doi: 10.1016/j.ejphar.2019.172525 PMID: 31288005
- Shi, G.H.; Zhou, L. Emodin suppresses angiogenesis and metastasis in anaplastic thyroid cancer by affecting TRAF6 mediated pathways in-vivo and in-vitro. Mol. Med. Rep., 2018, 18(6), 5191-5197. doi: 10.3892/mmr.2018.9510 PMID: 30272291
- Hao, D.C.; Xiao, P.G. Network pharmacology: A Rosetta Stone for traditional Chinese medicine. Drug Dev. Res., 2014, 75(5), 299-312. doi: 10.1002/ddr.21214 PMID: 25160070
- Zheng, J.; Wu, M.; Wang, H.; Li, S.; Wang, X.; Li, Y.; Wang, D.; Li, S. Network pharmacology to unveil the biological basis of health-strengthening herbal medicine in cancer treatment. Cancers, 2018, 10(11), 461. doi: 10.3390/cancers10110461 PMID: 30469422
- Kim, S.; Chen, J.; Cheng, T.; Gindulyte, A.; He, J.; He, S.; Li, Q.; Shoemaker, B.A.; Thiessen, P.A.; Yu, B.; Zaslavsky, L.; Zhang, J.; Bolton, E.E. PubChem 2023 update. Nucleic Acids Res., 2023, 51(D1), D1373-D1380. doi: 10.1093/nar/gkac956 PMID: 36305812
- Gallo, K.; Goede, A.; Preissner, R.; Gohlke, B.O. SuperPred 3.0: Drug classification and target predictiona machine learning approach. Nucleic Acids Res., 2022, 50(W1), W726-W731. doi: 10.1093/nar/gkac297 PMID: 35524552
- Daina, A.; Michielin, O.; Zoete, V. Swisstargetprediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res., 2019, 47(W1), W357-W364. doi: 10.1093/nar/gkz382 PMID: 31106366
- Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13. doi: 10.1186/1758-2946-6-13 PMID: 24735618
- Bateman, A.; Martin, M-J.; Orchard, S.; Magrane, M.; Agivetova, R.; Ahmad, S.; Alpi, E.; Bowler-Barnett, E.H.; Britto, R.; Bursteinas, B.; Bye-A-Jee, H.; Coetzee, R.; Cukura, A.; Da Silva, A.; Denny, P.; Dogan, T.; Ebenezer, T.G.; Fan, J.; Castro, L.G.; Garmiri, P.; Georghiou, G.; Gonzales, L.; Hatton-Ellis, E.; Hussein, A.; Ignatchenko, A.; Insana, G.; Ishtiaq, R.; Jokinen, P.; Joshi, V.; Jyothi, D.; Lock, A.; Lopez, R.; Luciani, A.; Luo, J.; Lussi, Y.; MacDougall, A.; Madeira, F.; Mahmoudy, M.; Menchi, M.; Mishra, A.; Moulang, K.; Nightingale, A.; Oliveira, C.S.; Pundir, S.; Qi, G.; Raj, S.; Rice, D.; Lopez, M.R.; Saidi, R.; Sampson, J.; Sawford, T.; Speretta, E.; Turner, E.; Tyagi, N.; Vasudev, P.; Volynkin, V.; Warner, K.; Watkins, X.; Zaru, R.; Zellner, H.; Bridge, A.; Poux, S.; Redaschi, N.; Aimo, L.; Argoud-Puy, G.; Auchincloss, A.; Axelsen, K.; Bansal, P.; Baratin, D.; Blatter, M-C.; Bolleman, J.; Boutet, E.; Breuza, L.; Casals-Casas, C.; de Castro, E.; Echioukh, K.C.; Coudert, E.; Cuche, B.; Doche, M.; Dornevil, D.; Estreicher, A.; Famiglietti, M.L.; Feuermann, M.; Gasteiger, E.; Gehant, S.; Gerritsen, V.; Gos, A.; Gruaz-Gumowski, N.; Hinz, U.; Hulo, C.; Hyka-Nouspikel, N.; Jungo, F.; Keller, G.; Kerhornou, A.; Lara, V.; Le Mercier, P.; Lieberherr, D.; Lombardot, T.; Martin, X.; Masson, P.; Morgat, A.; Neto, T.B.; Paesano, S.; Pedruzzi, I.; Pilbout, S.; Pourcel, L.; Pozzato, M.; Pruess, M.; Rivoire, C.; Sigrist, C.; Sonesson, K.; Stutz, A.; Sundaram, S.; Tognolli, M.; Verbregue, L.; Wu, C.H.; Arighi, C.N.; Arminski, L.; Chen, C.; Chen, Y.; Garavelli, J.S.; Huang, H.; Laiho, K.; McGarvey, P.; Natale, D.A.; Ross, K.; Vinayaka, C.R.; Wang, Q.; Wang, Y.; Yeh, L-S.; Zhang, J.; Ruch, P.; Teodoro, D. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res., 2021, 49(D1), D480-D489. doi: 10.1093/nar/gkaa1100 PMID: 33237286
- Amberger, J.S.; Bocchini, C.A.; Scott, A.F.; Hamosh, A. OMIM.org: Leveraging knowledge across phenotypegene relationships. Nucleic Acids Res., 2019, 47(D1), D1038-D1043. doi: 10.1093/nar/gky1151 PMID: 30445645
- Stelzer, G; Plaschkes, I; Oz-Levi, D; Alkelai, A; Olender, T; Zimmerman, S; Twik, M; Belinky, F; Fishilevich, S; Nudel, R VarElect: The phenotype-based variation prioritizer of the genecards suite. BMC Genomics, 2016, 17(Suppl 2), 444. doi: 10.1186/s12864-016-2722-2
- Piñero, J.; Ramírez-Anguita, J.M.; Saüch-Pitarch, J.; Ronzano, F.; Centeno, E.; Sanz, F.; Furlong, L.I. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res., 2020, 48(D1), D845-D855. PMID: 31680165
- Sherman, B.T.; Hao, M.; Qiu, J.; Jiao, X.; Baseler, M.W.; Lane, H.C.; Imamichi, T.; Chang, W. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res., 2022, 50(W1), W216-W221. doi: 10.1093/nar/gkac194 PMID: 35325185
- Meng, X.Y.; Zhang, H.X.; Mezei, M.; Cui, M. Molecular docking: A powerful approach for structure-based drug discovery. Curr. Computeraided Drug Des., 2011, 7(2), 146-157. doi: 10.2174/157340911795677602 PMID: 21534921
- Notarte, K.I.R.; Quimque, M.T.J.; Macaranas, I.T.; Khan, A.; Pastrana, A.M.; Villaflores, O.B.; Arturo, H.C.P.; Pilapil, D.Y.H., IV; Tan, S.M.M.; Wei, D.Q.; Wenzel-Storjohann, A.; Tasdemir, D.; Yen, C.H.; Ji, S.Y.; Kim, G.Y.; Choi, Y.H.; Macabeo, A.P.G. Attenuation of lipopolysaccharide-induced inflammatory responses through inhibition of the NF-κB pathway and the increased NRF2 level by a flavonol-enriched n -butanol fraction from uvaria alba. ACS Omega, 2023, 8(6), 5377-5392. doi: 10.1021/acsomega.2c06451 PMID: 36816691
- Quimque, M.T.; Notarte, K.I.; Letada, A.; Fernandez, R.A.; Pilapil, D.Y., IV; Pueblos, K.R.; Agbay, J.C.; Dahse, H.M.; Wenzel-Storjohann, A.; Tasdemir, D.; Khan, A.; Wei, D.Q.; Gose Macabeo, A.P. Potential cancer- and alzheimers disease-targeting phosphodiesterase inhibitors from uvaria alba: Insights from in vitro and consensus virtual screening. ACS Omega, 2021, 6(12), 8403-8417. doi: 10.1021/acsomega.1c00137 PMID: 33817501
- Carmo Bastos, M.L.; Silva-Silva, J.V.; Neves Cruz, J.; Palheta da Silva, A.R.; Bentaberry-Rosa, A.A.; da Costa Ramos, G.; de Sousa Siqueira, J.E.; Coelho-Ferreira, M.R.; Percário, S.; Santana Barbosa Marinho, P.; Marinho, A.M.R.; de Oliveira Bahia, M.; Dolabela, M.F. Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce apoptosis by caspase pathway in human gastric cancer cells. Pharmaceuticals, 2023, 16(5), 765. doi: 10.3390/ph16050765 PMID: 37242548
- de Almeida, R.B.M.; Barbosa, D.B.; do Bomfim, M.R.; Amparo, J.A.O.; Andrade, B.S.; Costa, S.L.; Campos, J.M.; Cruz, J.N.; Santos, C.B.R.; Leite, F.H.A.; Botura, M.B. Identification of a novel dual inhibitor of acetylcholinesterase and butyrylcholinesterase: In vitro and in silico studies. Pharmaceuticals, 2023, 16(1), 95. doi: 10.3390/ph16010095 PMID: 36678592
- Hiebl, V.; Ladurner, A.; Latkolik, S.; Dirsch, V.M. Natural products as modulators of the nuclear receptors and metabolic sensors LXR, FXR and RXR. Biotechnol. Adv., 2018, 36(6), 1657-1698. doi: 10.1016/j.biotechadv.2018.03.003 PMID: 29548878
- Ramos, INdF.; da Silva, MF.; Lopes, JMS.; Cruz, JN.; Alves, FS.; do Rego, JdAR.; Costa, MLd.; Assumpção, PPd.; Barros Brasil, DdS.; Khayat, AS. Extraction, characterization, and evaluation of the cytotoxic activity of piperine in its isolated form and in combination with chemotherapeutics against gastric cancer. Molecules, 2023, 28(14)
- Shahane, K.; Kshirsagar, M.; Tambe, S.; Jain, D.; Rout, S.; Ferreira, M.K.M.; Mali, S.; Amin, P.; Srivastav, P.P.; Cruz, J.; Lima, R.R. An updated review on the multifaceted therapeutic potential of calendula officinalis L. Pharmaceuticals, 2023, 16(4), 611. doi: 10.3390/ph16040611 PMID: 37111369
- Berger, S.I.; Iyengar, R. Network analyses in systems pharmacology. Bioinformatics, 2009, 25(19), 2466-2472. doi: 10.1093/bioinformatics/btp465 PMID: 19648136
- Macabeo, A.P.; Quimque, M.T.; Notarte, K.I.; Adviento, X.A.; Cabunoc, M.H.; de Leon, V.N.; delos Reyes, F.S.L.; Lugtu, E.J.; Manzano, J.A.; Monton, S.N.; Muñoz, J.E.; Ong, K.D.; Pilapil, D.Y.; Roque, V.; Tan, S.M.; Lim, J.A. Polyphenolic natural products active in silico against SARS-CoV-2 spike receptor binding domains and non-structural proteins - A review. Comb. Chem. High Throughput Screen., 2023, 26(3), 459-488. doi: 10.2174/1386207325666210917113207 PMID: 34533442
- Cui, W.; Aouidate, A.; Wang, S.; Yu, Q.; Li, Y.; Yuan, S. Discovering anti-cancer drugs via computational methods. Front. Pharmacol., 2020, 11, 733. doi: 10.3389/fphar.2020.00733 PMID: 32508653
- Huang, Z.; Yao, X.J.; Gu, R.X. Editorial: Computational approaches in drug discovery and precision medicine. Front Chem., 2021, 8, 639449. doi: 10.3389/fchem.2020.639449 PMID: 33659236
- Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7(1), 42717. doi: 10.1038/srep42717 PMID: 28256516
- Fernandez, R.A.; Quimque, M.T.; Notarte, K.I.; Manzano, J.A.; Pilapil, D.Y., IV; de Leon, V.N.; San Jose, J.J.; Villalobos, O.; Muralidharan, N.H.; Gromiha, M.M.; Brogi, S.; Macabeo, A.P.G. Myxobacterial depsipeptide chondramides interrupt SARS-CoV-2 entry by targeting its broad, cell tropic spike protein. J. Biomol. Struct. Dyn., 2022, 40(22), 12209-12220. doi: 10.1080/07391102.2021.1969281 PMID: 34463219
- Brogi, S.; Quimque, M.T.; Notarte, K.I.; Africa, J.G.; Hernandez, J.B.; Tan, S.M.; Calderone, V.; Macabeo, A.P. Virtual combinatorial library screening of quinadoline B derivatives against SARS-CoV-2 RNA-dependent RNA polymerase. Computation, 2022, 10(1), 7. doi: 10.3390/computation10010007
- Wu, G.; Wang, F.; Li, K.; Li, S.; Zhao, C.; Fan, C.; Wang, J. Significance of TP53 mutation in bladder cancer disease progression and drug selection. PeerJ, 2019, 7, e8261. doi: 10.7717/peerj.8261 PMID: 31871844
- Li, Q.Q.; Hao, J.J.; Zhang, Z.; Krane, L.S.; Hammerich, K.H.; Sanford, T.; Trepel, J.B.; Neckers, L.; Agarwal, P.K. Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics. Sci. Rep., 2017, 7(1), 201. doi: 10.1038/s41598-017-00143-6 PMID: 28298630
- Mason, R.A.; Morlock, E.V.; Karagas, M.R.; Kelsey, K.T.; Marsit, C.J.; Schned, A.R.; Andrew, A.S. EGFR pathway polymorphisms and bladder cancer susceptibility and prognosis. Carcinogenesis, 2009, 30(7), 1155-1160. doi: 10.1093/carcin/bgp077 PMID: 19372140
- Rubio, K.; Romero-Olmedo, A.J.; Sarvari, P.; Swaminathan, G.; Ranvir, V.P.; Rogel-Ayala, D.G.; Cordero, J.; Günther, S.; Mehta, A.; Bassaly, B.; Braubach, P.; Wygrecka, M.; Gattenlöhner, S.; Tresch, A.; Braun, T.; Dobreva, G.; Rivera, M.N.; Singh, I.; Graumann, J.; Barreto, G. Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer. Theranostics, 2023, 13(8), 2384-2407. doi: 10.7150/thno.79493 PMID: 37215577
- Hartleben, G.; Müller, C.; Krämer, A.; Schimmel, H.; Zidek, L.M.; Dornblut, C.; Winkler, R.; Eichwald, S.; Kortman, G.; Kosan, C.; Kluiver, J.; Petersen, I.; van den Berg, A.; Wang, Z.Q.; Calkhoven, C.F. Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitts lymphoma. EMBO J., 2018, 37(21), e98589. doi: 10.15252/embj.201798589 PMID: 30237309
- Jiménez-Vidal, L.; Espitia-Pérez, P.; Torres-Ávila, J.; Ricardo-Caldera, D.; Salcedo-Arteaga, S.; Galeano-Páez, C.; Pastor-Sierra, K.; Espitia-Pérez, L. Nuclear factor erythroid 2 related factor 2 and its relationship with cellular response in nickel exposure: A systems biology analysis. BMC Pharmacol. Toxicol., 2019, 20(S1)(Suppl. 1), 78. doi: 10.1186/s40360-019-0360-4 PMID: 31852525
- Lin, B.; Zhu, M.; Wang, W.; Li, W.; Dong, X.; Chen, Y.; Lu, Y.; Guo, J.; Li, M. Structural basis for alpha fetoprotein-mediated inhibition of caspase-3 activity in hepatocellular carcinoma cells. Int. J. Cancer, 2017, 141(7), 1413-1421. doi: 10.1002/ijc.30850 PMID: 28653316
- Lakhani, S.A.; Masud, A.; Kuida, K.; Porter, G.A., Jr; Booth, C.J.; Mehal, W.Z.; Inayat, I.; Flavell, R.A. Caspases 3 and 7: Key mediators of mitochondrial events of apoptosis. Science, 2006, 311(5762), 847-851. doi: 10.1126/science.1115035 PMID: 16469926
- Yamamura, M.; Sato, Y.; Takahashi, K.; Sasaki, M.; Harada, K. The cyclin-dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma. Oncol. Rep., 2020, 43(1), 306-317. PMID: 31746435
- Heo, J.; Lee, J.; Nam, Y.J.; Kim, Y.; Yun, H.; Lee, S.; Ju, H.; Ryu, C.M.; Jeong, S.M.; Lee, J.; Lim, J.; Cho, Y.M.; Jeong, E.M.; Hong, B.; Son, J.; Shin, D.M. The CDK1/TFCP2L1/ID2 cascade offers a novel combination therapy strategy in a preclinical model of bladder cancer. Exp. Mol. Med., 2022, 54(6), 801-811. doi: 10.1038/s12276-022-00786-0 PMID: 35729325
- Rehman, A.U.; Rahman, M.U.; Khan, M.T.; Saud, S.; Liu, H.; Song, D.; Sultana, P.; Wadood, A.; Chen, H.F. The landscape of protein tyrosine phosphatase (Shp2) and cancer. Curr. Pharm. Des., 2019, 24(32), 3767-3777. doi: 10.2174/1381612824666181106100837 PMID: 30398108
- Su, W.P.; Tu, I.H.; Hu, S.W.; Yeh, H.H.; Shieh, D.B.; Chen, T.Y.; Su, W.C. HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer. Biochem. Biophys. Res. Commun., 2007, 356(1), 181-186. doi: 10.1016/j.bbrc.2007.02.099 PMID: 17346677
- Martin-Way, D.; Puche-Sanz, I.; Cozar, J.M.; Zafra-Gomez, A.; Gomez-Regalado, M.D.C.; Morales-Alvarez, C.M.; Hernandez, A.F.; Martinez-Gonzalez, L.J.; Alvarez-Cubero, M.J. Genetic variants of antioxidant enzymes and environmental exposures as molecular biomarkers associated with the risk and aggressiveness of bladder cancer. Sci. Total Environ., 2022, 843, 156965. doi: 10.1016/j.scitotenv.2022.156965 PMID: 35764155
- Dash, S.; Sahu, A.K.; Srivastava, A.; Chowdhury, R.; Mukherjee, S. Exploring the extensive crosstalk between the antagonistic cytokines- TGF-β and TNF-α in regulating cancer pathogenesis. Cytokine, 2021, 138, 155348. doi: 10.1016/j.cyto.2020.155348 PMID: 33153895
- Cruceriu, D.; Baldasici, O.; Balacescu, O.; Berindan-Neagoe, I. The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: Molecular insights and therapeutic approaches. Cell Oncol., 2020, 43(1), 1-18. doi: 10.1007/s13402-019-00489-1 PMID: 31900901
- Hao, J.; Zhang, W.; Huang, Z. Bupivacaine modulates the apoptosis and ferroptosis in bladder cancer via phosphatidylinositol 3-kinase (PI3K)/AKT pathway. Bioengineered, 2022, 13(3), 6794-6806. doi: 10.1080/21655979.2022.2036909 PMID: 35246010
- Yang, G.; Li, Z.; Dong, L.; Zhou, F. lncRNA ADAMTS9-AS1 promotes bladder cancer cell invasion, migration, and inhibits apoptosis and autophagy through PI3K/AKT/mTOR signaling pathway. Int. J. Biochem. Cell Biol., 2021, 140, 106069. doi: 10.1016/j.biocel.2021.106069 PMID: 34428588
- Chi, M.; Liu, J.; Mei, C.; Shi, Y.; Liu, N.; Jiang, X.; Liu, C.; Xue, N.; Hong, H.; Xie, J.; Sun, X.; Yin, B.; Meng, X.; Wang, B. TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer. J. Exp. Clin. Cancer Res., 2022, 41(1), 175. doi: 10.1186/s13046-022-02377-3 PMID: 35581606
- Gourisankar, S.; Krokhotin, A.; Ji, W.; Liu, X.; Chang, C.Y.; Kim, S.H.; Li, Z.; Wenderski, W.; Simanauskaite, J.M.; Yang, H.; Vogel, H.; Zhang, T.; Green, M.R.; Gray, N.S.; Crabtree, G.R. Rewiring cancer drivers to activate apoptosis. Nature, 2023, 620(7973), 417-425. doi: 10.1038/s41586-023-06348-2 PMID: 37495688
- Jia, X.; Wen, Z.; Sun, Q.; Zhao, X.; Yang, H.; Shi, X.; Xin, T. Apatinib suppresses the proliferation and apoptosis of gastric cancer cells via the PI3K/Akt signaling pathway. J. BUON, 2019, 24(5), 1985-1991. PMID: 31786865
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