Effects of Selective COX-Inhibitors and Classical NSAIDs on Endothelial Cell Proliferation and Migration Induced by Human Cholangiocarcinoma Cell Culture
Sookruetai Boonmasawai DVM*, Pravit Akarasereenont MD, PhD*, Kitirat Techatraisak MD, PhD**, Athiwat Thaworn BSc*, Sirikul Chotewuttakorn MSc*, Titchaporn Palo BSc*
Affiliation : * Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand ** Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
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-CM-
induced 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
