Anti-cutaneous squamous cell carcinoma effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m / 中国药房

ABSTRACT

OBJECTIVE To study the effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m on cutaneous squamous cell carcinoma. METHODS Using human cutaneous squamous cell carcinoma A431 and Colo-16 cells as research subjects， CCK-8 assay was used to detect the effects of different concentrations of 3m （5， 10， 20， 40， 80 μmol/L） on the proliferation of A431 and Colo-16 cells after 24， 48 and 72 hours； the median inhibitory concentration （IC50） was calculated at 48 h of treatment. A431 and Colo-16 cells were divided into control group， 3m low-concentration and high- concentration groups （15， 30 μmol/L）. After treated with relevant drugs or culture medium for 48 h， the morphological changes of cells in each group were observed by inverted microscope. Clone formation rate， migration rate and number of cell invasions， cell cycle distribution and apoptosis rate were detected. The phosphorylation， or expression of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway related proteins [JAK2， STAT3， B-cell lymphocyte-2 （Bcl-2）， Bcl-2- associated X protein （Bax）]， and their mRNA expression in cells were detected. RESULTS 3m could significantly inhibit the proliferation of A431 and Colo-16 cells after treated for 24， 48， 72 h （P＜0.01）， and IC50 of them were 20.36， 23.72 μmol/L， respectively. After 48 hours of treatment， compared with control group， A431 and Colo-16 cells arranged sparsely and loosely connected in 3m low-concentration and high-concentration groups. The clone formation rate， migration rate， number of cell invasions， mRNA expressions of JAK2， STAT3 and Bcl-2， the phosphorylation of JAK2 and STAT3， protein expression of Bcl-2 were significantly decreased/weakened （P＜0.01）. Proportion of cell cycle in G2 phase， apoptosis rate， protein and mRNA expression of Bax were increased significantly （P＜0.01）； and all the above effects were in dose-dependent manner. CONCLUSIONS 3m can inhibit the proliferation， clone formation， migration and invasion abilities of cutaneous squamous cell carcinoma A431 and Colo-16 cells in a dose-dependent manner， the mechanism of which may be associated with inhibiting the activity of JAK2/STAT3 signaling pathway， and inducing cell apoptosis.