Hyperoside exhibits anticancer activity in non‑small cell lung cancer cells with T790M mutations by upregulating FoxO1 via CCAT1.

Abstract

Acquired epidermal growth factor receptor (EGFR) T790M mutation is the most common mechanism that accounts for EGFR‑TKI (tyrosine kinase inhibitor) resistance of non‑small cell lung cancer (NSCLC). High expense and acquired resistance weaken support for the use of osimertinib for T790M‑positive NSCLC treatment, and limit the efficacy and application of this drug. Hyperoside, a flavonol glycoside compound, extracted from Hypericum perforatum, has been reported to inhibit the growth of a variety of tumors. The present study aimed to investigate the role of hyperoside in treating NSCLC with T790M mutations, and to elucidate the underlying molecular mechanisms. Cell viability assays, apoptosis analysis, reverse transcription‑quantitative PCR, western blot analysis, animal experiments and immunohistochemistry were performed to examine the anticancer activity of hyperoside. Hyperoside inhibited the proliferation and induced the apoptosis of T790M‑positive NSCLC cells. Hyperoside upregulated forkhead box proteinO1 (FoxO1) expression and downregulated the level of long non‑coding RNA (lncRNA) colon cancer associated transcript1 (CCAT1) in T790M‑positive NSCLC cells. In the invivo study, hyperoside inhibited the growth of T790M‑positive NSCLC xenografts. In conclusion, hyperoside inhibited proliferation and induced apoptosis by upregulating FoxO1 via CCAT1 in T790M‑positive NSCLC both invitro and invivo, suggesting that hyperoside is a novel candidate for T790M‑positive NSCLC treatment.