Tanshinone reverses androgen deprivation-induced invasion of prostate cancer cells by suppressing PI3K and AKT signaling pathways
Objective:To explore the effect of tanshinone on the invasion of PCa cells induced by androgen-deprivation therapy(ADT)and its possible action mechanism.Methods:We treated human PCa LNCaP cells with tanshinone at 0 nmol/L(the control group),5 nmol/L(tanshinone group 1),10 nmol/L(tanshinone group 2)and 20 nmol/L(tanshinone group 3),respectively.Then we detected their cloning,angiogenesis and invasion abilities by plate cloning assay,tube-formation assay and Transwell chamber as-say,respectively,examined their apoptosis using the AnnexinV-FITC/PI double staining method,and determined the protein expres-sions of phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT)and p-AKT by Western blot.Results:Compared with the control group,the PCa LNCaP cells in the tanshinone groups 1,2 and 3 showed significant dose-dependent decreases in the clone formation rate([25.14±5.19]%vs[19.33±4.12]%vs[14.69±4.71]%vs[9.35±2.37]%,P<0.05),number of cellular lumens([23.20±4.85]vs[19.80±5.12]vs[14.40±4.16]vs[10.20±3.21]per microscopic field,P<0.05)and count of transmembrane cells([62.80±8.97]vs[50.40±7.62]vs[38.60±5.16]vs[27.40±4.91]per micro-scopic field,P<0.05),increase in the rate of cell apoptosis([3.58±0.74]%vs[8.97±1.36]%vs[14.64±4.10]%vs[21.17±5.37]%,P<0.05),and down-regulation of the expressions of p-PI3K,PI3K,p-AKT and AKT(P<0.05).Conclu-sion:Tanshinone can reverse ADT-induced invasion of PCa cells,reduce their clone formation and angiogenesis,promote their apopto-sis,and inhibit the activity of PI3K and AKT signaling pathways.