奥西默替尼
蛋白激酶B
PI3K/AKT/mTOR通路
肺癌
体内
癌症研究
T790米
细胞凋亡
药理学
医学
癌症
化学
吉非替尼
表皮生长因子受体
生物
内科学
生物化学
生物技术
埃罗替尼
作者
Lei Lai,Qiuping Shen,Yingjie Wang,Liting Chen,Jianjun Lai,Zhibing Wu,Hao Jiang
标识
DOI:10.1016/j.taap.2021.115518
摘要
Lung cancer is considered the main cause of cancer mortality worldwide. Osimertinib, a third-generation EGFR-TKI, 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 osimertinib-resistant 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.
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