title: A preclinical study on the combination therapy of everolimus and transarterial chemoembolization in hepatocellular carcinoma.
abstract: Transarterial chemoembolization (TACE) is commonly used for the treatment of locally advanced hepatocellular carcinoma (HCC) by its dual effects of chemotherapy and ischemic hypoxia. However, one of the side effects of TACE is the introduction of hypoxic condition, which in turn activates hypoxia-induced survival pathways and enhances VEGF-induced neovascularization by stabilizing HIF-1α expression. Herein, the preclinical therapeutic efficacy of the combined treatment of everolimus, a novel mTOR inhibitor and TACE for the treatment of HCC was investigated. The MHCC-97L cells were used for the study of the effect of combined treatment on cell proliferation and cellular apoptosis. HUVEC cells were used for the study on tube formation under different treatments. Inhibitions on the Akt/mTOR pathways were also studied. Finally, the effect on tumor growth was further study using an in vivo orthotopic model. The results demonstrated that everolimus enhanced the therapeutic efficacy of TACE in inhibiting cell proliferation, promoting apoptosis and inhibiting tube formation of endothelial cells by blocking the Akt/mTOR signaling pathway in vitro and inhibiting tumor growth and neoangiogenesis in vivo. Based on this preclinical study, the potential of combining everolimus with TACE was guaranteed which suggested the use of the combination therapy in the clinical treatment of advanced HCC patients.
authors.affiliation: Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong Hong Kong, China.
authors.forename: Ariel Km
authors.initials: AK
authors.lastname: Chow
authors.affiliation: Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong Hong Kong, China.
authors.forename: Thomas Cc
authors.initials: TC
authors.lastname: Yau
authors.affiliation: Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong Hong Kong, China.
authors.forename: Lui
authors.initials: L
authors.lastname: Ng
authors.affiliation: Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong Hong Kong, China.
authors.forename: Andrew Cy
authors.initials: AC
authors.lastname: Chu
authors.affiliation: Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong Hong Kong, China.
authors.forename: Wai-Lun
authors.initials: WL
authors.lastname: Law
authors.affiliation: Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong Hong Kong, China.
authors.forename: Ronnie Tp
authors.initials: RT
authors.lastname: Poon
authors.affiliation: Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong Hong Kong, China.
authors.forename: Roberta Wc
authors.initials: RW
authors.lastname: Pang
keywords: Everolimus; hepatocellular carcinoma; hypoxia; mTOR signaling pathway; transarterial chemoembolization; tumor growth