[Impact of hypoxia on taxol-induced apoptosis in human ovarian cancer cell line A2780 and its mechanism].

OBJECTIVE

Hypoxia, a feature and important living microenvironment of solid tumors, might be related to drug-resistance of tumors. This study was to establish a hypoxic model of ovarian cancer cell line A2780, and to investigate impacts of hypoxia and hypoxia inducible factor-1alpha (HIF-1alpha) on Taxol-induced apoptosis in A2780 cells.

METHODS

Cobalt chloride (CoCl(2)), a chemical hypoxia inducer, was added in A2780 cells to develop a hypoxic model. A2780 cells were divided into 4 groups: group A (control), group B (normoxia plus Taxol), group C (hypoxia plus Taxol), and group D (hypoxia, Decoy plus Taxol). Decoy method was used to block the function of HIF-1alpha. Protein and mRNA levels of HIF-1alpha were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL), and flow cytometry (FCM).

RESULTS

CoCl(2) evidently increased protein level of HIF-1alpha, but had no effect on mRNA level of HIF-1alpha. Decoy didn't affect its expression. TUNEL showed that apoptotic index (AI) was significantly higher in group B,and group D than in group C after treatment of Taxol [(41.1+/-25.6)%,and (35.2+/-21.7)% vs. (24.1+/-15.2)%, P < 0.05]. The apoptosis rates detected by FCM displayed the same tendency as TUNEL results did.

CONCLUSIONS

Hypoxia could weaken the effect of Taxol on inducing apoptosis of A2780 cells. HIF-1alpha might confer to resistance of cell apoptosis induced by Taxol.