title: Anti-proliferative action of IL-6R-targeted antibody tocilizumab for non-small cell lung cancer cells.
abstract: In the present study we analyzed the anti-proliferative effect of tocilizumab, a humanized recombinant monoclonal interleukin 6 receptor (IL-6R) antibody, against non-small cell lung cancer (NSCLC) cells, including A549, H460, H358 and H1299 cells. The cell cycle distribution of NSCLCs was analyzed using fluorescence-activated cell sorting and gene expression using quantitative polymerase chain reaction. Cell lysates treated with tocilizumab were immunoblotted with antibodies against signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, extracellular-signal-regulated kinases (ERK), phospho-ERK, nuclear factor κB (NFκB) and phospho-NFκB. Significant growth inhibition of NSCLC cells was observed following treatment with tocilizumab. Proliferation was significantly decreased by approximately 10-40% in A549, H460, H1299 and H358 cells, with an inhibition rate that was comparable with that of the typical anticancer drugs methotrexate and 5-fluorouracil. NSCLC cell populations were accumulated in the sub-G1 phase by treatment with tocilizumab. Western blot analyses revealed a possible activation of the NFκB pathway by tocilizumab. Overall, these data indicate that tocilizumab has anticancer potency via apoptosis induction as an agonistic IL-6R regulator. Therefore, we suggest that this anti-IL-6R antibody may be utilized as a new targeting molecule for NSCLC therapies.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Na-Hyun
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Seong-Kwan
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Dong-Soon
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Park
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Yi
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Jin-Suk
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin
keywords: NFκB; anti-proliferation; interleukin 6 signaling; non-small cell lung cancer; tocilizumab