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

Shuliu Sang; Chenbing Sun; Rongzhen Ding; Jingjie Jiang; Yang Han; Shanshan Gan; Ling Bi; Yabin Gong

doi:10.3389/fphar.2022.1019451

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

Front Pharmacol. 2022 Nov 29:13:1019451. doi: 10.3389/fphar.2022.1019451. eCollection 2022.

Authors

Shuliu Sang¹, Chenbing Sun¹, Rongzhen Ding^{1

2}, Jingjie Jiang¹, Yang Han¹, Shanshan Gan¹, Ling Bi¹, Yabin Gong¹

Affiliations

¹ Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Institutional Key Laboratory of Vascular Biology and Translational Medicine in Hunan Province, Hunan University of Chinese Medicine, Changsha, China.

Abstract

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.

Keywords: Feiyanning formula; Wnt/β-catenin pathway; drug resistance; lung cancer; osimertinib.