Synergistic effect of targeting the epidermal growth factor receptor and hyaluronan synthesis in oesophageal squamous cell carcinoma cells.

background and purposeWorldwide, oesophageal cancer is the eighth most common cancer and has a very poor survival rate. In order to identify new tolerable treatment options for oesophageal squamous cell carcinoma (ESCC), erlotinib was tested with moderate efficacy in phase I and II studies. As 4-methylumbelliferone (4-MU), an hyaluronan (HA) synthesis inhibitor showed anti-cancer effects in vitro, and in ESCC xenograft tumours, we investigated whether the anti-cancer effects of erlotinib could be augmented by combining it with 4-MU. EXPERIMENTAL APPROACH: ESCC cell lines were treated with erlotinib or gefitinib (1 μmol·L KEY

resultsThe combination of erlotinib and 4-MU synergistically inhibited the proliferation of ESCC cell lines. Furthermore, the migration speed of ESCC cell line KYSE-410 in gap closure assays was significantly reduced by the combination of erlotinib and 4-MU. Decreased ERK phosphorylation could explain the anti-proliferative and anti-migratory effects in the combined treatment group. Finally, the combination was additionally able to decrease the growth of multicellular tumour spheroids, a three-dimensional cell culture model that was associated with sustained inhibition of ERK1/2 phosphorylation. CONCLUSIONS AND IMPLICATIONS: The combination of 4-MU and erlotinib showed promising anti-cancer efficacies in the ESCC cell lines.