Effects of a protein kinase C inhibitor combined with cisplatin on non-small cell lung cancer

Abstract

To study the effects and possible mechanisms of the protein kinase C (PKC) inhibitor chelerythrine chloride (CH), combined with cisplatin (DDP) on human non-small cell lung cancer. The effect of CH, DDP and the combination on proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT assay and flow cytometry respectively. The inhibitory effects of CH and DDP on neoplasia were verified on subcutaneous implanted tumor of nude mice. Implanted tumor models were constructed in nude mice using human lung adenocarcinoma cell line A549. Twenty-four BALB/c nude mice with implanted tumors were divided into 4 groups randomly: group CH, group DDP, group CH + DDP, and normal saline group (group NS), each with 5 mice. CH, DDP or NS were intraperitoneally injected into nude mice for 3 weeks (DDP or NS was injected once a week, CH was injected twice a week). CH inhibited A549 cell proliferation in a concentration-dependent pattern. When CH and DDP were combined, the inhibitory effect was enhanced in a synergistic or additive pattern. Both CH and DDP significantly increased the apoptosis of A549 cells, and this action was remarkably increased when DDP was combined with CH. CH and DDP inhibited the growth of subcutaneous implanted tumor in nude mice and the inhibitory rate of group CH + DDP (80.5%) was significantly higher than that of group CH (72.4%) or group DDP (64.3%) (t = 11.34, P < 0.01). CH combined with DDP shows significantly synergistic anti-tumor effects on non-small cell lung cancer cell line A549 and subcutaneous implanted tumor in nude mice, possibly by enhancement of growth inhibition and apoptosis induction on tumor cells.