Effects of selective COX-inhibitors and classical NSAIDs on endothelial cell proliferation and migration induced by human cholangiocarcinoma cell culture

Experiments were designed to explore cellular mechanisms and effects of NSAIDs on human umbilical vein endothelial cells (HUVEC) induced by human cholangiocarcinoma (HuCCA). HUVEC were incubated with HuCCA or HuCCA-conditioned medium (CM) for various times to determine cell proliferation and migration. Expression of cyclooxygenase (COX) proteins was measured using immunoblotting technique. VSA (selective COX-1 inhibitor), NS-398 (selective COX-2 inhibitor), and aspirin were used as pharmacological tools to explore signaling mechanisms of HuCCA-CM-induced endothelial cell functions. HuCCA could significantly induce proliferation and migration of HUVEC. COX-2, but not COX-1, was increased. NS-398, but not VSA, could significantly inhibit HuCCA-CM-induced endothelial cell proliferation. HuCCA-CM-induced endothelial cell proliferations could be also inhibited by aspirin. These findings suggest that HuCCA-CM-derived substances could induce HUVEC proliferation through COX-2 signaling mechanism. Classical NSAID and selective COX-2 inhibitors could also inhibit this step of HUVEC proliferation.