Synergistic effects of BAY606583 on docetaxel in esophageal cancer through modulation of ERK1/2.

Abstract

Docetaxel (DTX) is a taxane chemotherapy agent used to treat many types of cancers, including esophageal squamous cell carcinoma. Adenosine is a purinergic signaling molecule that contributes to cancercellproliferation via A2B adenosine receptor (A2BAR) activation. Extracellular signal-regulated protein kinase (ERK) plays a crucial role in cell proliferation in various types of cancers. Stimulation of A2BAR involves a regulated ERK signaling pathway, and might provide a fascinating approach for treatment, leading to decreased proliferation in certain tumors that express A2BAR. Recent studies demonstrated that DTX and A2BAR have anticancer effects. The current study was designed to investigate the synergistic effect of the A2BAR agonist (BAY606583) on DTX in inducing antiproliferation effects on esophageal squamous cells carcinoma (ESCCs). The cell viability was assessed using the MTT assay in KYSE-30 and Ym-1 cells. In addition, the synergistic effect of DTX on the A2BAR agonist was evaluated. Subsequently, apoptosis was assessed by Annexin-V and propidium iodide staining, and Bcl-2, Bax, and ERK1/2 protein-level expressions were evaluated by Western blot. Use of BAY606583 and cotreatment of DTX and BAY606583 significantly decreased cell proliferation in KYSE-30 and Ym-1 cell lines. The use of BAY606583 and cotreatment of DTX with the A2BAR agonist induced apoptosis in KYSE-30 and Ym-1 cells. Western blot analysis revealed that the use of the A2BAR agonist and cotreatment of DTX with the A2BAR agonist inhibited the expression of apoptotic regulatory proteins as well as the expression of ERK1/2 proteins. Our findings suggested that use of BAY606583 and cotreatment of BAY606583/DTX have an antiproliferative effect on ESCC cell lines through ERK signaling pathway inhibition. BAY606583 has a synergistic effect on DTX, which could be used as an adjuvant for esophageal cancer therapy.