A novel sensitizer reduces EGFR-TKI resistance by regulating the PI3K/Akt/mTOR pathway and autophagy

The incidence and mortality of lung cancer are high, and treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the preferred first-line treatment for patients suffering from non-small cell lung cancer (NSCLC) with EGFR mutations. However, EGFR-TKI resistance leads to treatment failure. Yifei-Sanjie pill (YFSJ) is a novel type of Chinese patent medicine for lung cancer. The development of YFSJ has progressed for more than 30 years; however, little is known about the molecular mechanisms associated with the inhibition of drug resistance.

In this study, flow cytometry and transcriptome sequencing were used in vitro to explore the anticancer effect of Yifei-Sanjie pill (YFSJ) on EGFR-TKI-resistant cell lines and to identify potential molecular mechanisms associated with the inhibition of drug resistance.

We found that in vitro, YFSJ and YFSJ combined with gefitinib significantly reduced the viability of H1975 and H1650 cells, which is dose-dependent at 24 and 48 h. PI3K, Akt and mTOR were downregulated, while after 24 and 48 h of treatment with YFSJ alone and in combination with gefitinib, LC3A and LC3B were up-regulated in both cell lines.

YFSJ reduced the viability of EGFR-TKI-resistant cell lines, reducing resistance to gefitinib. This might be caused by a decrease in the PI3K/Akt/mTOR pathway and an increase in autophagy.