The Role of Emodin in the Treatment of Bladder Cancer Based on Network Pharmacology and Experimental Verification


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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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. Gallo, K.; Goede, A.; Preissner, R.; Gohlke, B.O. SuperPred 3.0: Drug classification and target prediction—a machine learning approach. Nucleic Acids Res., 2022, 50(W1), W726-W731. doi: 10.1093/nar/gkac297 PMID: 35524552
  11. 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
  12. 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
  13. 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
  14. Amberger, J.S.; Bocchini, C.A.; Scott, A.F.; Hamosh, A. OMIM.org: Leveraging knowledge across phenotype–gene relationships. Nucleic Acids Res., 2019, 47(D1), D1038-D1043. doi: 10.1093/nar/gky1151 PMID: 30445645
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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 alzheimer’s 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
  21. 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
  22. 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
  23. 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
  24. 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)
  25. 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
  26. Berger, S.I.; Iyengar, R. Network analyses in systems pharmacology. Bioinformatics, 2009, 25(19), 2466-2472. doi: 10.1093/bioinformatics/btp465 PMID: 19648136
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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 Burkitt’s lymphoma. EMBO J., 2018, 37(21), e98589. doi: 10.15252/embj.201798589 PMID: 30237309
  38. 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
  39. 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
  40. 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
  41. 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
  42. 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
  43. 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
  44. 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
  45. 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
  46. 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
  47. 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
  48. 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
  49. 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
  50. 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
  51. 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
  52. 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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