Anti-proliferative action of IL-6R-targeted antibody tocilizumab for non-small cell lung cancer cells

作者：Kim Na Hyun; Kim Seong Kwan; Kim Dong Soon; Zhang Dan; Park Jin A; Yi Hee; Kim Jin Suk; Shin Ho Chul^*

来源：Oncology Letters, 2015, 9(5): 2283-2288.

DOI：10.3892/ol.2015.3019

• tocilizumab
• interleukin 6 signaling
• non-small cell lung cancer
• NF kappa B
• anti-proliferation

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 kappa B (NF kappa B) and phospho-NF kappa B. 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 NF kappa B 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.

• 出版日期2015-5