Effect of doxycycline on the proliferation of human small cell lung cancer H446 cells in vitro and its mechanisms / 国际药学研究杂志

ABSTRACT

Objective To investigate the effect of doxycycline on the proliferation of human small cell lung cancer H446 cells in vitro and its possible mechanisms. Methods H446 cells were treated with different concentrations of doxycycline for 24,48,72 or 96 h. Cell proliferation was measured by CCK-8 assay,IC50 was caculated by Bliss,and cell apoptosis was examined by TUNEL assay. The protein and mRNA expression of Bcl-2 and Bax in H446 cells were detected by Western blot and real time-PCR,respectively. Re-sults Doxycycline inhibited the proliferation of H446 cells in a concentration-time dependent manner. The half inhibitory concentra-tions(IC50)of doxycycline on cell proliferation in H446 cells were approximately 24.10 mg/L for 24 h treatment group,10.98 mg/L for 48 h treatment group,8.20 mg/L for 72 h treatment group and 8.03 mg/L for 96 h treatment group,respectively. Furthermore,doxycy-cline treatment could also induce the apoptosis of H446 cells in a concentration-dependent manner. Moreover,doxycycline treatment dramatically down-regulated the expression of Bcl-2 and up-regulated the expression of Bax in H446 cells both at the protein and at the mRNA levels. The differences were statistically significant(P<0.05). Conclusion Doxycycline can inhibit the proliferation of H446 cells by inducing apoptosis via down-regulating the expression of Bcl-2 and up-regulating the expression of Bax. Doxycycline has great potential as a chemotherapeutic agent for human small cell lung cancer.