Establishment of Docetaxel Resistant Variant of Human Lung Adenocarcinoma Cell Line A549/DTX and Its Resistance Mechanism

Objective To establish a human lung adenocarcinoma cell line A549 with the characterization of docetaxel (DTX) resistance, and investigate its biological mechanism of drug resistance. Methods A DTX resistant human lung adenocarcinoma cell line A549/DTX was obtained discontinuously by gradually increasing doses of DTX. The drug resistance of A549/DTX was evaluated by MTT assay. Apoptosis rates of DTX resistant human lung adenocarcinoma cell line A549/DTX and parental cell line A549 were detected by fl ow cytometry (FCM). The expression levels of Bc1-2 and Bax protein of the two cel1 1ines induced by different concentrations of DTX were detected by Western blot. Results Resistance index(IR) of A549/DTX was 18.5. The apoptosis rates induced by 12.5, 25 and 50 μg/L of DTX were (6.2±4.1)％, (13.6±2.7)％ and (20.5±5.1)％ in A549/DTX cells, signifi cantly lower than that in A549 cells which were (15.7 ±3.5)％, (28.5±2.9)％ and (33.1±4.8)％ respectively（P＜0.01）. Western blot showed a statistically higher expression of Bc1-2 and lower expression of Bax in A549/DTX than that in A549 cells at protein levels (P＜0.01) . Conclusion A drug-resistant cell line A549/DTX with high IR was established by discontinuously induction and gradually increasing doses of DTX. Apoptosis inhibition is one of the mechanisms underlying the drug resistance of human lung adenocarcinoma cell line A549/DTX and is related with the up-regulation of Bc1-2 expression and down-regulation of Bax expression.