热休克蛋白90
蛋白激酶B
化学
PI3K/AKT/mTOR通路
Hsp90抑制剂
癌症研究
信号转导
热休克蛋白
生物化学
生物
基因
作者
Xiaoli Li,Guoli Wang,Xiaolin Zhou,Haitao Zhao,Xiaojie Chen,Qixiao Cui,Minjing Li,Guanhua Xue,Xiaoyü Wei,Lei Ye,Defang Li,Hong Pan
摘要
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Thus, the development of safe and effective therapeutic compounds for GC treatment is urgently required. Here, we aimed to examine the role of picropodophyllin (PPP), a compound extracted from the rhizome of Dysosma versipellis (Hance) M. Cheng ex Ying, on the proliferation of GC cells. Our study revealed that PPP inhibits the proliferation of GC cells in a dose-dependent manner by inducing apoptosis. Moreover, our study elucidated that PPP suppresses the growth of GC tumor xenografts with no side effects of observable toxicity. Mechanistically, PPP exerts its effects by blocking the AKT/mammalian target of rapamycin (mTOR) signaling pathway; these effects are markedly abrogated by the overexpression of constitutively active AKT. Furthermore, drug affinity responsive target stability (DARTS) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) revealed that heat shock protein 90 (HSP90) may be a potential target of PPP. Surface plasmon resonance and immunoprecipitation assay validated that PPP directly targets HSP90 and disrupts the binding of HSP90 to AKT, thereby suppressing GC cell proliferation. Thus, our study revealed that PPP may be a promising therapeutic compound for GC treatment.
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