Background:
Adenosine released by cancer cells in high amounts in the tumour microenvironment is
one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological
control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the
methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer
cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive
and cisplatin-resistant ovarian cancer cells to cisplatin treatment.
Methods:
The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin
cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/
antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis
events and cisplatin incorporation in cancer cells were determined.
Results:
PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from
low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the
opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin
cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring
mitochondrial and plasma membrane potentials that were disturbed by cisplatin.
Conclusion:
Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells
resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell
biology should be considered in the context of supportive chemotherapy for ovarian cancer.
Susana Godinho: Placing cell biology at the center of cancer research
