title: An anti-transferrin receptor antibody enhanced the growth inhibitory effects of chemotherapeutic drugs on human non-hematopoietic tumor cells.
abstract: Transferrin receptor (TfR) has been used as a target for antibody-based therapy of cancer. Combining anti-TfR antibodies with chemotherapeutic drugs shows potential as one of the strategies for cancer therapy. In this study, we investigated the effects of anti-TfR monoclonal antibody 7579 alone or in combination with chemotherapeutic drugs (5-fluorouracil or doxorubicin) on non-hematopoietic tumor cells (HepG2 and MCF-7) in vitro. We found that 7579 mAb alone could dramatically down-regulate surface TfR expression on tumor cells. Consequently, marked S phase arrest and apoptosis were observed in 7579 mAb-treated tumor cells. In combination with 5-fluorouracil or doxorubicin, 7579 mAb enhanced the growth inhibitory effects of chemotherapeutic drugs on tumor cells. Results of 7AAD/Annexin V staining demonstrated that 7579 mAb enhanced the cytotoxic effects of chemotherapeutic drugs on tumor cells by mainly promoting tumor cell necrosis. Using the median-effect/combination-index isobologram method, we further evaluated the nature of 7579 mAb/chemotherapeutic drug interactions. Synergistic interaction was observed for 7579 mAb combined with 5-fluorouracil whereas additive efficacy was observed for 7579 mAb plus doxorubicin. Our study provided the basis to further develop 7579 mAb-containing chemoimmunotherapy for non-hematopoietic malignancies.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shen
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Zhu
authors.forename: Feng-Rong
authors.initials: FR
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Xing-Fei
authors.initials: XF
authors.lastname: Pan
authors.forename: Ping
authors.initials: P
authors.lastname: Lei
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Wang
authors.forename: Guan-Xin
authors.initials: GX
authors.lastname: Shen
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D011990:Receptors, Transferrin; D004317:Doxorubicin; D005472:Fluorouracil