title: Differential combined effect of COX inhibitors on cell survival suppressed by sorafenib in the HepG2 cell line.
abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib, a molecular-targeted drug, is a multi-target oral anti-neoplastic drug that is used as a first-line treatment for patients with advanced Human HCC. An increase in the expression of the cyclooxygenase-2 (COX-2) protein and sequential production of prostaglandin (PG) E2 were previously shown to significantly enhance carcinogenesis. Although the synergistic and/or additive effects of various COX inhibitors have been demonstrated in HCC, those of a combination of sorafenib and COX inhibitors remain unclear. The aim of the present study was to examine the antitumor effects of a combination of sorafenib and COX inhibitors on HCC HepG2 cells. Various COX inhibitors suppressed HepG2 cell survival, and exhibited a combined effect with sorafenib. However, COX-2 selectivity had little relevance. The co-administration of COX inhibitors and sorafenib increased the frequency of apoptosis. Moreover, the combination of sorafenib and diclofenac significantly increased Bax protein expression levels. The results of the present study indicate that COX inhibitors can be administered in combination with sorafenib for HCC therapy.
authors.affiliation: Department of Pharmacy, Okayama University Hospital.
authors.forename: Kenta
authors.initials: K
authors.lastname: Yagi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakamura
authors.forename: Taro
authors.initials: T
authors.lastname: Miura
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Takeda
authors.forename: Satoru
authors.initials: S
authors.lastname: Esumi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsunaga
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sendo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib