Effects of PHPO on apoptosis and proliferation of lung cancer cell line A549 / 上海交通大学学报（医学版）

ABSTRACT

Objective · To investigate the effect of a new type of allene compound, 1-phenylpropadienyl phosphine oxide (PHPO), on proliferation and apoptosis of lung cancer cell line A549. Methods · A549 cells were treated with different concentrations of PHPO. The effects of PHPO on cell proliferation, apoptosis and cell cycle were detected by CCK-8 and flow cytometry assay. Wound healing test was used to measure the migration ability of A549 cells. Real-time PCR was used to detect the expression of apoptosis and cell cycle related gene. The expression of proteins in MAPK pathway was assayed by the Western blotting. The nude mice xenograft model of human lung cancer A549 cells was established. After tumor formation, PHPO was injected daily for treatment, and the tumor size was observed. Results · Compared to the control group, PHPO significantly inhibited the cell viability of A549 cells and induced apoptosis of them, and the IC50 value of 24 h is 44.23 μmol/L. PHPO blocked the cell cycle in the G1 phase significantly. The migration capacity of PHPO-treated cells was decreased. The mRNA levels of Bax and P21 were up-regulated in PHPO-treated group, and the mRNA lever of Bcl-2 was down-regulated (P<0.05). PHPO increased the phosphorylation levels of p38, ERK and JNK. Injection of PHPO could significantly inhibit the growth of tumor in the xenograft model compared to the control group (P<0.05). Conclusion · PHPO can induce the apoptosis and inhibit the proliferation of A549 cells, block the cell cycle in the G1 phase and decrease the migration ability of A549 cells significantly. The mechanism may be related to the activation of MAPK signaling pathway by PHPO and the increase of phosphorylation of p38, ERK and JNK.