Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells via IL-6/STAT3 Pathway Inhibition

Biological & Pharmaceutical Bulletin
Wei LouJun Wang

Abstract

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has linked the epithelial-mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties. In the current work, we aimed to testify whether PPI could reverse EMT and overcome acquired EGFR-TKI resistance. We exposed HCC827 lung adenocarcinoma cells to erlotinib which resulted in acquired resistance with strong features of EMT. PPI effectively restored drug sensitivity of cells that obtained acquired resistance. PPI reversed EMT and decreased interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway activation in erlotinib-resistant cells. Moreover, addition of IL-6 partially abolished the sensitization response of PPI. Furthermore, co-treatment of erlotinib and PPI completed abrogation of tumor growth in xenografts,...Continue Reading

References

May 1, 1990·Molecular and Cellular Biology·T A Libermann, D Baltimore
Jan 8, 1999·Japanese Journal of Clinical Oncology·T YamaguchiT Ogura
Dec 25, 2004·Cancer Letters·Jenny Yuen-Nei CheungSiu-Kai Kong
Dec 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert L YauchLukas C Amler
Jun 17, 2010·Nature Reviews. Clinical Oncology·Deric L WheelerPaul M Harari
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Zhan YaoRaffaella Sordella
Oct 28, 2010·Acta Biochimica Et Biophysica Sinica·Minjian KongRongzhen Xu
Mar 25, 2011·Science Translational Medicine·Lecia V SequistJeffrey A Engelman
Mar 25, 2011·Nature·Trever G BivonaCharles L Sawyers
May 21, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kenichi SudaTetsuya Mitsudomi
Jan 31, 2012·The Lancet Oncology·Rafael RosellUNKNOWN Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia T
Jul 4, 2012·Nature Genetics·Zhenfeng ZhangTrever G Bivona
Jul 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kadoaki OhashiWilliam Pao
Oct 24, 2012·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Fariz NurwidyaKazuhisa Takahashi
Dec 12, 2013·The Journal of Pharmacy and Pharmacology·Lina WuYong Liu
Mar 20, 2014·The Journal of Clinical Investigation·Matjaz RokavecHeiko Hermeking
Mar 20, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Li LiYong He
Aug 29, 2014·Journal of Cancer Research and Clinical Oncology·Entidhar Al SawahPatricia L Judson
Oct 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Helena A YuChristine M Lovly
Apr 30, 2015·The New England Journal of Medicine·Pasi A JänneMalcolm Ranson
May 16, 2015·Cancer Metastasis Reviews·Stefan Zimmermann, Solange Peters
Aug 6, 2015·The New England Journal of Medicine·Lecia V SequistAndrew R Allen
Aug 6, 2015·The New England Journal of Medicine·Yong He
Dec 26, 2015·Advances in Experimental Medicine and Biology·Vivek Mittal
Jul 28, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bowen Du, Joong Sup Shim
Sep 14, 2016·Bioorganic & Medicinal Chemistry Letters·Jing LiuWenyuan Gao
Nov 10, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yanxia LiXiaodong Ma
Jan 21, 2017·Oncology Letters·Linhui GuWei Yu

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Citations

Apr 1, 2018·Thoracic Cancer·Zuoqing SongYuxin Wang
Aug 17, 2019·Frontiers in Pharmacology·Lorena Avila-CarrascoGuadalupe González Mateo
Dec 25, 2019·Chemico-biological Interactions·Ye TianMei-Yun Fang
Dec 12, 2020·Drug Discovery Today·Po-Chang Shih, Kuo-Ching Mei

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