Epidermal growth factor receptor (EGFR) is considered as a valid target in the clinical trials of anticancer therapy and tyrosine kinase inhibitors (TKIs) of EGFR are approved for cancer treatments. In present work, cucurbitacin IIb (CuIIb) was confirmed to exhibit the proliferation inhibitory activity in A549 cells. CuIIb induced apoptosis via STAT3 pathway, which was mitochondria-mediated and caspase-dependent. CuIIb also suppressed the cell cycle and induced G2/M phase cell cycle arrest. CuIIb was capable of suppressing the signal transmitting of the EGFR/mitogen-activated protein kinase (MAPK) pathway which was responsible for the apoptosis and cell cycle arrest. Homogeneous time-resolved fluorescence (HTRF) analysis demonstrated that the kinase activity of EGFR was inhibited by CuIIb. Molecular docking suggested that the CuIIb-EGFR binding fundamentally depends on the contribution of both hydrophobic and hydrogen-bonding interactions. Hence CuIIb may serve as a potential EGFR TKI.

在抗癌疗法的临床试验中，表皮生长因子受体（EGFR）被认为是有效的靶标，EGFR的酪氨酸激酶抑制剂（TKIs）已获批准用于癌症治疗。在目前的工作中，葫芦素IIb（CuIIb）被证实在A549细胞中具有增殖抑制活性。CuIIb通过STAT3途径诱导细胞凋亡，该途径是线粒体介导的和caspase依赖性的。CuIIb还抑制细胞周期并诱导G2 / M期细胞周期停滞。CuIIb能够抑制导致细胞凋亡和细胞周期停滞的EGFR /丝裂原活化蛋白激酶（MAPK）途径的信号传递。均相时间分辨荧光（HTRF）分析表明，CuIIb抑制了EGFR的激酶活性。分子对接表明，CuIIb-EGFR结合从根本上取决于疏水和氢键相互作用的贡献。因此，CuIIb可作为潜在的EGFR TKI。