title: Sinomenine hydrochloride enhancement of the inhibitory effects of anti-transferrin receptor antibody-dependent on the COX-2 pathway in human hepatoma cells.
abstract: Transferrin receptor (TfR) has been used as a target for the antibody-based therapy of cancer due to its higher expression in tumors relative to normal tissues. Great potential has been shown by anti-TfR antibodies combined with chemotherapeutic drugs as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with sinomenine hydrochloride in vitro. Results suggested that anti-TfR mAb or sinomenine hydrochloride could induce apoptosis, inhibit proliferation, and affect the cell cycle. A synergistic effect was found in relation to tumor growth inhibition and the induction of apoptosis when anti-TfR mAb and sinomenine hydrochloride were used simultaneously. The expression of COX-2 and VEGF protein in HepG2 cells treated with anti-TfR mAb alone was increased in line with increasing dosage of the agent. In contrast, COX-2 expression was dramatically decreased in HepG2 cells treated with sinomenine hydrochloride alone. Furthermore, we demonstrated that the inhibitory effects of sinomenine hydrochloride and anti-TfR mAb administered in combination were more prominent than when the agents were administered singly. To sum up, these results showed that the combined use of sinomenine hydrochloride and anti-TfR mAb may exert synergistic inhibitory effects on human hepatoma HepG2 cells in a COX-2-dependent manner. This finding provides new insight into how tumor cells overcome the interference of iron intake to survive and forms the basis of a new therapeutic strategy involving the development of anti-TfR mAb combined with sinomenine hydrochloride for liver cancer.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hongkong Road, Wuhan, 430030, People's Republic of China. hongyiwh@sina.com
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.forename: Huifen
authors.initials: H
authors.lastname: Zhu
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Sun
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.forename: Jing
authors.initials: J
authors.lastname: Bian
authors.forename: Heyu
authors.initials: H
authors.lastname: Hu
authors.forename: Lu
authors.initials: L
authors.lastname: Yuan
authors.forename: Juan
authors.initials: J
authors.lastname: Tao
authors.forename: Ping
authors.initials: P
authors.lastname: Lei
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000628:therapy*; D009019:Morphinans / Q000494:pharmacology* / Q000627:therapeutic use; D011990:Receptors, Transferrin / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D009019:Morphinans; D011990:Receptors, Transferrin; D042461:Vascular Endothelial Growth Factor A; C009271:sinomenine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human