The Dual Effects of Δ⁹-Tetrahydrocannabinol on Cholangiocarcinoma Cells: Anti-Invasion Activity at Low Concentration and Apoptosis Induction at High Concentration

Abstract

Currently, only gemcitabine plus platinum demonstrates the considerable activity for cholangiocarcinoma. The anticancer effect of Δ 9-tetrahydrocannabinol (THC), the principal active component of cannabinoids has been demonstrated in various kinds of cancers. We therefore evaluate the antitumor effects of THC on cholangiocarcinoma cells. Both cholangiocarcinoma cell lines and surgical specimens from cholangiocarcinoma patients expressed cannabinoid receptors. THC inhibited cell proliferation, migration and invasion, and induced cell apoptosis. THC also decreased actin polymerization and reduced tumor cell survival in anoikis assay. pMEK1/2 and pAkt demonstrated the lower extent than untreated cells. Consequently, THC is potentially used to retard cholangiocarcinoma cell growth and metastasis.