Aurothiomalate sodium is a potent and selective inhibitor of oncogenic PKCι signalling. Aurothiomalate sodium inhibits tumour cell proliferation but not apoptosis. Aurothiomalate sodium is a potent inhibitor of TrxR. Aurothiomalate sodium is an antirheumatic drug with strong antitumour activity[1][2][3].At concentrations of 0.001, 0.01, 0.1, 1, 10, 100, and 1000 uM, Aurothiomalate sodium induced inhibition of anchorage-independent growth in a dose-dependent manner in subject cell lines with IC50 of 300 nM-107 µM. Aurothiomalate sodium can induce inhibition of anchorage-independent growth in a dose-dependent manner with an IC50 of 300 nM-107 µM, including the A549, H1437, H2170, H460, H510, H187, H1703, and A427 lung cancer cell lines. Lung adenocarcinoma (LAC) and small cell lung cancer (SCLC) cells were more sensitive to Aurothiomalate sodium, while lung adenocarcinoma (LAC) was less sensitive to Aurothiomalate sodium. Aurothiomalate sodium blocked PKCι-Par6- by binding PKCι Rac1-Pak-Mek 1,2-Erk 1,2 signalling pathway activation and inhibits the growth of non-small lung cancer (NSCLC)[1].Aurothiomalate sodium inhibits TNFα-induced NF-kB activation and the expression of NF-kB-targeted pro-inflammatory genes (e.g., E-selectin and COX-2) at a concentration of 25 uM for 6 hours[3].
Aurothiomalate sodium 动物研究
Animal study
Aurothiomalate sodium administered intramuscularly at doses of 2, 6, 20 or 60 mg/kg/day for 40 days had a statistically significant inhibitory effect on tumour growth in A427 cell tumours at all concentrations tested as A427 cells showing highly response[1].At 20 and 60 mg/kg/day, administered intramuscularly for 15 days, Aurothiomalate sodium showed statistically significant inhibition of H460 tumours only at the 60 mg/kg dose because of the low response of H460 cells[1].Aurothiomalate sodium reduced tumour growth in three-week-old KrasLA2 mice when administered intraperitoneally at a dose of 60 mg/kg/day for six weeks. Aurothiomalate sodium inhibited Kras-mediated expansion of bronchioalveolar stem cells (BASCs) and lung tumourigenesis in vivo[2].
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