STAT3 inhibitor in combination with irradiation significantly inhibits cell viability, cell migration, invasion and tumorsphere growth of human medulloblastoma cells

References

• Allen C, Her S, Jaffray DA. 2017. Radiotherapy for Cancer: present and Future. Adv Drug Deliv Rev. 109:1–2. 10.1016/j.addr.2017.01.004.
   PubMed Web of Science ®Google Scholar
• Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro Oncol. 2019;21:v1–v100. 10.1093/neuonc/noz150.
   PubMed Web of Science ®Google Scholar
• Millard NE, De Braganca KC. 2016. Medulloblastoma. J Child Neurol. 31:1341–1353. 10.1177/0883073815600866.
   PubMed Web of Science ®Google Scholar
• Packer RJ, Cogen P, Vezina G, Rorke LB. 1999. Medulloblastoma: clinical and biologic aspects. Neuro Oncol. 1:232–250. 10.1093/neuonc/1.3.232.
   PubMedGoogle Scholar
• Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, Eden C, Kranenburg TA, Hogg T, Poppleton H, Martin J, et al. 2010. Subtypes of medulloblastoma have distinct developmental origins. Nature. 468(7327):1095–1099. DOI:10.1038/nature09587
   PubMed Web of Science ®Google Scholar
• Gilbertson RJ, Ellison DW. 2008. The origins of medulloblastoma subtypes. Annu Rev Pathol. 3:341–365. 10.1146/annurev.pathmechdis.3.121806.151518.
   PubMed Web of Science ®Google Scholar
• Padovani L, Horan G, Ajithkumar T. 2019. Radiotherapy Advances in Paediatric Medulloblastoma Treatment. Clin Oncol (R Coll Radiol). 31:171–181. 10.1016/j.clon.2019.01.001.
   PubMed Web of Science ®Google Scholar
• Ris MD, Packer R, Goldwein J, Jones-Wallace D, Boyett JM. 2001. Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children’s Cancer Group study. J Clin Oncol. 19:3470–3476. 10.1200/jco.2001.19.15.3470.
   PubMed Web of Science ®Google Scholar
• Kamran MZ, Patil P, Gude RP. 2013. Role of STAT3 in cancer metastasis and translational advances. Biomed Res Int. 2013:421821. 10.1155/2013/421821.
   PubMed Web of Science ®Google Scholar
• Lee H, Jeong AJ, Ye SK. 2019. Highlighted STAT3 as a potential drug target for cancer therapy. BMB Rep. 52:415–423. 10.5483/BMBRep.2019.52.7.152.
   PubMed Web of Science ®Google Scholar
• Furtek SL, Backos DS, Matheson CJ, Strategies RP. 2016. Approaches of Targeting STAT3 for cancer treatment. ACS Chem Biol. 11:308–318. 10.1021/acschembio.5b00945.
   PubMed Web of Science ®Google Scholar
• Debnath B, Xu S, Neamati N. 2012. Small molecule inhibitors of signal transducer and activator of transcription 3 (Stat3) protein. J Med Chem. 55:6645–6668. 10.1021/jm300207s.
   PubMed Web of Science ®Google Scholar
• Schaefer LK, Ren Z, Fuller GN, Schaefer TS. 2002. Constitutive activation of Stat3alpha in brain tumors: localization to tumor endothelial cells and activation by the endothelial tyrosine kinase receptor (VEGFR-2). Oncogene. 21:2058–2065. 10.1038/sj.onc.1205263.
   PubMed Web of Science ®Google Scholar
• Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res. 2002;8:945–954.
   PubMed Web of Science ®Google Scholar
• Garg N, Bakhshinyan D, Venugopal C, Mahendram S, Rosa DA, Vijayakumar T, Manoranjan B, Hallett R, McFarlane N, Delaney KH, et al. 2017. CD133(+) brain tumor-initiating cells are dependent on STAT3 signaling to drive medulloblastoma recurrence. Oncogene. 36:606–617. 10.1038/onc.2016.235.
   PubMed Web of Science ®Google Scholar
• White CL, Jayasekara WSN, Picard D, Chen J, Watkins DN, Cain JE, Remke M. Gough DJ. A sexually dimorphic role for STAT3 in Sonic Hedgehog Medulloblastoma. Cancers (Basel). 2019;11. doi:10.3390/cancers11111702.
   PubMed Web of Science ®Google Scholar
• Ajeawung NF, Wang HY, Gould P, Kamnasaran D. 2012. Advances in molecular targets for the treatment of medulloblastomas. Clin Invest Med. 35:E246. 10.25011/cim.v35i5.18697.
   PubMed Web of Science ®Google Scholar
• Wei J, Ma L, Li C, Pierson CR, Finlay JL, Lin J. 2019. Targeting upstream kinases of STAT3 in human medulloblastoma cells. Curr Cancer Drug Targets. 19:571–582. 10.2174/1568009618666181016165604.
   PubMed Web of Science ®Google Scholar
• Ball S, Li C, Li PK, Lin J. 2011 The small molecule, LLL12, inhibits STAT3 phosphorylation and induces apoptosis in medulloblastoma and glioblastoma cells. PLoS One. 6:e18820. 10.1371/journal.pone.0018820
   Google Scholar
• Xiao H, Bid HK, Jou D, Wu X, Yu W, Li C, Houghton PJ, Lin J. 2015. A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells. J Biol Chem. 290:3418–3429. 10.1074/jbc.M114.616748.
   PubMed Web of Science ®Google Scholar
• Qin JJ, Yan L, Zhang J, Zhang WD. 2019. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review. J Exp Clin Cancer Res. 38:195. 10.1186/s13046-019-1206-z.
   PubMed Web of Science ®Google Scholar
• Yu W, Li C, Zhang W, Xia Y, Li S, Lin JY, Yu K, Liu M, Yang L, Luo J, et al. 2017. Discovery of an orally selective inhibitor of signal transducer and activator of transcription 3 using advanced multiple ligand simultaneous docking. J Med Chem. 60:2718–2731. 10.1021/acs.jmedchem.6b01489.
   PubMed Web of Science ®Google Scholar
• Xie B, Zhang L, Hu W, Fan M, Jiang N, Duan Y, Jing D, Xiao W, Fragoso RC, Lam KS, et al. Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells. Redox Biol. 2019;24:101189. 10.1016/j.redox.2019.101189.
   PubMed Web of Science ®Google Scholar
• Oweida AJ, Darragh L, Phan A, Binder D, Bhatia S, Mueller A, Court BV, Milner D, Raben D, Woessner R, et al. STAT3 modulation of regulatory T cells in response to radiation therapy in head and neck cancer. J Natl Cancer Inst. 2019;111:1339–1349. 10.1093/jnci/djz036.
   PubMedGoogle Scholar
• Kim KW, Mutter RW, Cao C, Albert JM, Shinohara ET, Sekhar KR, Lu B. Inhibition of signal transducer and activator of transcription 3 activity results in down-regulation of survivin following irradiation. Mol Cancer Ther. 2006;5:2659–2665. 10.1158/1535-7163.mct-06-0261.
   PubMed Web of Science ®Google Scholar
• Spitzner M, Roesler B, Bielfeld C, Emons G, Gaedcke J, Wolff HA, Rave-Fränk M, Kramer F, Beissbarth T, Kitz J, et al. 2014. Overexpression of STAT3 potentiates growth, survival, and radioresistance of non-small-cell lung cancer (NSCLC) cells. Int J Cancer. 134:997–1007. 10.1002/ijc.28429.
   PubMed Web of Science ®Google Scholar
• Yin ZJ, Jin FG, Liu TG, Fu EQ, Xie YH, Sun RL. 2011. Overexpression of STAT3 potentiates growth, survival, and radioresistance of non-small-cell lung cancer (NSCLC) cells. J Surg Res. 171:675–683. 10.1016/j.jss.2010.03.053.
   PubMed Web of Science ®Google Scholar
• Bonner JA, Trummell HQ, Willey CD, Plants BA, Raisch KP. 2009. Inhibition of STAT-3 results in radiosensitization of human squamous cell carcinoma. Radiother Oncol. 92:339–344. 10.1016/j.radonc.2009.06.022.
   PubMed Web of Science ®Google Scholar
• Spitzner M, Ebner R, Wolff HA, Ghadimi BM, Wienands J, Grade M. 2014. STAT3: a novel molecular mediator of resistance to chemoradiotherapy. Cancers (Basel). 6:1986–2011. 10.3390/cancers6041986.
   PubMed Web of Science ®Google Scholar
• Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, et al. 2011. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol. 29:1408–1414. 10.1200/jco.2009.27.4324.
   PubMed Web of Science ®Google Scholar
• Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109. 10.1007/s00401-007-0243-4.
   PubMed Web of Science ®Google Scholar
• Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, et al. 2012. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 123:465–472. 10.1007/s00401-011-0922-z.
   PubMed Web of Science ®Google Scholar
• Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803–820. 10.1007/s00401-016-1545-1.
   PubMed Web of Science ®Google Scholar
• Liu X, Ding C, Tan W, Zhang A. Medulloblastoma: Molecular understanding, treatment evolution, and new developments. Pharmacol Ther. 2020;210:107516. 10.1016/j.pharmthera.2020.107516
   Google Scholar
• You S, Li R, Park D, Xie M, Sica GL, Cao Y, Xiao Z-Q, Deng X. 2014. Disruption of STAT3 by niclosamide reverses radioresistance of human lung cancer. Mol Cancer Ther. 13:606–616. 10.1158/1535-7163.mct-13-0608.
   PubMed Web of Science ®Google Scholar
• Kim JS, Kim HA, Seong MK, Seol H, Oh JS, Kim EK, Chang JW, Hwang S-G, Noh WC. 2016. STAT3-survivin signaling mediates a poor response to radiotherapy in HER2-positive breast cancers. Oncotarget. 7:7055–7065. 10.18632/oncotarget.6855.
   PubMedGoogle Scholar
• Park SY, Lee CJ, Choi JH, Kim JH, Kim JW, Kim JY, Nam JS. The JAK2/STAT3/CCND2 Axis promotes colorectal Cancer stem cell persistence and radioresistance. J Exp Clin Cancer Res. 2019;38:399. 10.1186/s13046-019-1405-7.
   PubMed Web of Science ®Google Scholar
• Wang X, Zhang X, Qiu C, Yang N. 2020. STAT3 contributes to radioresistance in cancer. Front Oncol. 10:1120. 10.3389/fonc.2020.01120.
   PubMed Web of Science ®Google Scholar
• Otero DC, Poli V, David M, Rickert RC. 2006. Cutting edge: inherent and acquired resistance to radiation-induced apoptosis in B cells: a pivotal role for STAT3. J Immunol. 177:6593–6597. 10.4049/jimmunol.177.10.6593.
   PubMed Web of Science ®Google Scholar
• Ivanov DP, Coyle B, Walker DA, Grabowska AM. 2016. In vitro models of medulloblastoma: choosing the right tool for the job. J Biotechnol. 236:10–25. 10.1016/j.jbiotec.2016.07.028.
   PubMed Web of Science ®Google Scholar
• Martirosian V, Chen TC, Lin M, Neman J. 2016. Medulloblastoma initiation and spread: where neurodevelopment, microenvironment and cancer cross pathways. J Neurosci Res. 94:1511–1519. 10.1002/jnr.23917.
   PubMed Web of Science ®Google Scholar
• Entschladen F, TLt D, Lang K, Joseph J, Zaenker KS. 2004. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters. Lancet Oncol. 5:254–258. 10.1016/s1470-2045(04)01431-7.
   PubMed Web of Science ®Google Scholar
• Nalla AK, Asuthkar S, Bhoopathi P, Gujrati M, Dinh DH, Rao JS. Suppression of uPAR retards radiation-induced invasion and migration mediated by integrin β1/FAK signaling in medulloblastoma. PLoS One. 2010;5:e13006. 10.1371/journal.pone.0013006
   Google Scholar
• Rieken S, Rieber J, Brons S, Habermehl D, Rief H, Orschiedt L, Lindel K, Weber KJ, Debus J, Combs SE. Radiation-induced motility alterations in medulloblastoma cells. J Radiat Res. 2015;56:430–436. 10.1093/jrr/rru120.
   PubMed Web of Science ®Google Scholar
• Konings K, Vandevoorde C, Belmans N, Vermeesen R, Baselet B, Walleghem MV, Janssen A, Isebaert S, Baatout S, Haustermans K. The combination of particle irradiation with the Hedgehog inhibitor GANT61 differently modulates the radiosensitivity and migration of cancer cells compared to X-ray irradiation. Front Oncol. 2019;9:391. 10.3389/fonc.2019.00391.
   PubMed Web of Science ®Google Scholar
• Asuthkar S, Nalla AK, Gondi CS, Dinh DH, Gujrati M, Mohanam S, Rao JS. 2011. Gadd45a sensitizes medulloblastoma cells to irradiation and suppresses MMP-9-mediated EMT. Neuro Oncol. 13:1059–1073. 10.1093/neuonc/nor109.
   PubMed Web of Science ®Google Scholar
• Visvader JE, Lindeman GJ. 2008. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 10.1038/nrc2499.
   PubMed Web of Science ®Google Scholar
• Najafi M, Mortezaee K, Majidpoor J. 2019. Cancer stem cell (CSC) resistance drivers. Life Sci. 234:116781. 10.1016/j.lfs.2019.116781.
   PubMed Web of Science ®Google Scholar
• Lu KH, Chen YW, Tsai PH, Tsai ML, Lee YY, Chiang CY, Kao C-L, Chiou S-H, Ku -H-H, Lin C-H, et al. 2009. Evaluation of radiotherapy effect in resveratrol-treated medulloblastoma cancer stem-like cells. Childs Nerv Syst. 25:543–550. 10.1007/s00381-009-0826-6.
   PubMed Web of Science ®Google Scholar
• Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. 2004. Identification of human brain tumour initiating cells. Nature. 432(7015):396–401. 10.1038/nature03128.
   PubMed Web of Science ®Google Scholar
• Chang CJ, Chiang CH, Song WS, Tsai SK, Woung LC, Chang CH, Jeng S-Y, Tsai C-Y, Hsu -C-C, Lee H-F, et al. 2012. Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells. Childs Nerv Syst. 28:363–373. 10.1007/s00381-011-1672-x.
   PubMed Web of Science ®Google Scholar
• Yang MY, Lee HT, Chen CM, Shen CC, Ma HI. 2014. Celecoxib suppresses the phosphorylation of STAT3 protein and can enhance the radiosensitivity of medulloblastoma-derived cancer stem-like cells. Int J Mol Sci. 15:11013–11029. 10.3390/ijms150611013.
   PubMed Web of Science ®Google Scholar