Lapatinib induced cell cycle arrest and apoptosis in CNE-2z cells / 解放军医学杂志

ABSTRACT

Objective To explore the effect of lapatinib on the cell cycle and apoptosis of human CNE-2Z nasopharyngeal carcinoma (NPC) cells, and to study the related mechanisms. Methods CCK-8 assay was used to assess the proliferation of CNE-2Z cells treated by lapatinib. After PI staining, the cell cycle distribution was determined by flow cytometry. Apoptosis was analyzed using Annexin V/PI double binding assay. The mRNA expression of cell cycle related molecular Cyclin D1, P21 and P53 was assessed with real time PCR. The expression of protein Cyclin D1, P21, P53, and apoptosis related protein Mcl-1 and Bax was determined by Western blotting. The enzymatic activity of caspase-3/7 was measured by using Apo-ONE Homogeneous Caspase-3/7 Assay kit. Results Lapatinib inhibited the proliferation of CNE-2Z cells in a dose-dependent manner. Various concentrations of lapatinib induced significant G0/G1 phase arrest and promoted apoptosis of CNE-2Z cells. Lapatinib significantly down-regulated Cyclin D1 expression, but up-regulated P21 and P53 expression at mRNA and protein levels. Lapatinib also induced down-regulation of Mcl-1 with up-regulation of Bax protein expression, and activated Caspase-3/7 in CNE-2Z cells. Conclusion Lapatinib may effectively inhibit proliferation, induce cell cycle arrest and promote apoptosis of CNE-2Z cells, so it may serve as a potent therapeutic agent against nasopharyngeal carcinoma.