Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway

Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival a...

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Main Authors: Shuliu Sang, Chenbing Sun, Rongzhen Ding, Jingjie Jiang, Yang Han, Shanshan Gan, Ling Bi, Yabin Gong
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.1019451/full
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author Shuliu Sang
Chenbing Sun
Rongzhen Ding
Rongzhen Ding
Jingjie Jiang
Yang Han
Shanshan Gan
Ling Bi
Yabin Gong
author_facet Shuliu Sang
Chenbing Sun
Rongzhen Ding
Rongzhen Ding
Jingjie Jiang
Yang Han
Shanshan Gan
Ling Bi
Yabin Gong
author_sort Shuliu Sang
collection DOAJ
description Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3β and SRFS1, which are enriched in the Wnt/β-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/β-catenin pathway.
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spelling doaj.art-1261223b8d8b4195af5e0dee775b0e782022-12-22T03:44:22ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10194511019451Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathwayShuliu Sang0Chenbing Sun1Rongzhen Ding2Rongzhen Ding3Jingjie Jiang4Yang Han5Shanshan Gan6Ling Bi7Yabin Gong8Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitutional Key Laboratory of Vascular Biology and Translational Medicine in Hunan Province, Hunan University of Chinese Medicine, Changsha, ChinaDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaFeiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3β and SRFS1, which are enriched in the Wnt/β-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/β-catenin pathway.https://www.frontiersin.org/articles/10.3389/fphar.2022.1019451/fullFeiyanning formulaosimertinibdrug resistancelung cancerWnt/β-catenin pathway
spellingShingle Shuliu Sang
Chenbing Sun
Rongzhen Ding
Rongzhen Ding
Jingjie Jiang
Yang Han
Shanshan Gan
Ling Bi
Yabin Gong
Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway
Frontiers in Pharmacology
Feiyanning formula
osimertinib
drug resistance
lung cancer
Wnt/β-catenin pathway
title Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway
title_full Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway
title_fullStr Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway
title_full_unstemmed Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway
title_short Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway
title_sort feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the wnt β catenin pathway
topic Feiyanning formula
osimertinib
drug resistance
lung cancer
Wnt/β-catenin pathway
url https://www.frontiersin.org/articles/10.3389/fphar.2022.1019451/full
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