Polyphyllin I reverses the resistance of osimertinib in non-small cell lung cancer cell through regulation of PI3K/Akt signaling

Lung cancer is considered the main cause of cancer mortality worldwide. Osimertinib, a third-generation EGFRTKI, has been approved and administrated for treating patients with either EGFR T790M mutation or EGFR sensitive mutation. However, resistance to osimertinib emerges and has been considered to be the main obstacle in lung cancer treatment. Polyphyllin I is isolated from the natural herb Paris polyphylla and exhibits anti-cancer activities. In the present study, we identify Polyphyllin I to reverse the resistance of osimertinib in vitro and in vivo. The results showed that Polyphyllin I reversed the resistance of osimertinib through promoting apoptosis, modulating the PI3K/Akt signaling, and regulating the expression of apoptosis-related proteins in osimertinibresistant cell lines. In vivo study confirmed the results, showing that the tumor growth was significantly suppressed in the Polyphyllin I/osimertinib group compared to the osimertinib group. It has been clarified that Polyphyllin I could reverse the resistance of osimertinib in osimertinib-resistant non-small cell of lung cancer in vitro and in vivo. The underlying mechanism might be related to the downregulation of the PI3K/Akt signaling and increase of the expression of apoptosis-related proteins, suggesting that Polyphyllin I was a promising therapeutic agent for reversing the resistance of osimertinib.