Effects of Selective COX-Inhibitors and Classical NSAIDs on Endothelial Cell Proliferation and Migration Induced by Human Cholangiocarcinoma Cell Culture

Objective: Experiments were designed to explore cellular mechanisms and effects of NSAIDs on human umbilical vein endothelial cells (HUVEC) induced by human cholangiocarcinoma (HuCCA). Material and Method: 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-CMinduced endothelial cell functions. Results: 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. Conclusion: 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. Keywords: Cholangiocarcinoma/ HUVEC/Proliferation/ COX-2/ NSAIDs