Cisplatin resistance is a major challenge in the clinical treatment of
ovarian cancer, of which the underlying mechanisms remain unknown. The aim of the present study was to explore the role of autophagy in
cisplatin resistance in
ovarian cancer cells. A2780cp
cisplatin-resistant ovarian
carcinoma cells and the A2780 parental cell line, were used as a model throughout the present study. The cell viability was determined using a water soluble tetrazolium salt-8 assay, and western blot analysis was performed to determine the
protein expression levels of
microtubule-associated protein 1 light chain 3 (LC3 I and LC3 II), and
Beclin 1.
Beclin 1 small interfering (si)
RNA and
3-methyladenine (3-MA) were used to determine whether inhibition of autophagy may re-sensitize
cisplatin-resistant cells to
cisplatin. The ultrastructural analysis of autophagosomes was performed using transmission electron microscopy, and apoptosis was measured by flow cytometry. In both A2780cp and A2780 cells,
cisplatin induced the formation of autophagosomes and upregulated the expression levels of autophagy
protein markers, LC3 II and
Beclin 1. However, the levels of autophagy were significantly higher in A2780cp cells, as compared with the A2780 cells. The combined treatment of
cisplatin with 3-MA, the autophagy pharmacological inhibitor, increased the cell death rate, but had no effects on apoptosis, as compared with
cisplatin treatment alone in A2780cp cells. However, inhibition of autophagy by
siRNA knockdown of
Beclin 1 expression enhanced
cisplatin-induced cell death and apoptosis. The findings of the present study suggest that autophagy has a protective role in human
ovarian cancer cells, and that targeting autophagy may promote chemotherapeutic sensitivity.