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Article

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

  • Authors:
    • Na‑Hyun Kim
    • Seong‑Kwan Kim
    • Dong‑Soon Kim
    • Dan Zhang
    • Jin‑A Park
    • Hee Yi
    • Jin‑Suk Kim
    • Ho‑Chul Shin
  • View Affiliations / Copyright

    Affiliations: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea
  • Pages: 2283-2288
    |
    Published online on: March 9, 2015
       https://doi.org/10.3892/ol.2015.3019
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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.
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1 

Lam WK and Watkins DN: Lung cancer: future directions. Respirology. 12:471–477. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Kishimoto T, Akira S, Narazaki M and Taga T: Interleukin-6 family of cytokines and gp130. Blood. 86:1243–1254. 1995.PubMed/NCBI

3 

Hodge DR, Hurt EM and Farrar WL: The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer. 41:2502–2512. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Michalaki V, Syrigos K, Charles P and Waxman J: Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer. 90:2312–2316. 2004.PubMed/NCBI

5 

Plante M, Rubin SC, Wong GY, Federici MG, Finstad CL and Gastl GA: Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer. 73:1882–1888. 1994. View Article : Google Scholar : PubMed/NCBI

6 

Zhang GJ and Adachi I: Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res. 19:1427–1432. 1999.PubMed/NCBI

7 

Chung YC and Chang YF: Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol. 83:222–226. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Ohsugi Y and Kishimoto T: The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis. Expert Opin Biol Ther. 8:669–681. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Bongartz T: Tocilizumab for rheumatoid and juvenile idiopathic arthritis. Lancet. 371:961–963. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Kudo M, Jono H, Shinriki S, Yano S, Nakamura H, Makino K, Hide T, Muta D, Ueda M, Ota K, et al: Antitumor effect of humanized anti-interleukin-6 receptor antibody (tocilizumab) on glioma cell proliferation. Laboratory investigation. J Neurosurg. 111:219–225. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Haura EB, Livingston S and Coppola D: Autocrine interleukin-6/interleukin-6 receptor stimulation in non-small-cell lung cancer. Clin Lung Cancer. 7:273–275. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Yi H, Cho HJ, Cho SM, Jo K, Park JA, Kim NH, Amidon GL, Kim JS and Shin HC: Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells. Int J Oncol. 41:310–316. 2012.PubMed/NCBI

13 

Koyama Y, Mitsui N, Suzuki N, Yanagisawa M, Sanuki R, Isokawa K, Shimizu N and Maeno M: Effect of compressive force on the expression of inflammatory cytokines and their receptors in osteoblastic Saos-2 cells. Arch Oral Biol. 53:488–496. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Jiang XP, Yang DC, Elliott RL and Head JF: Down-regulation of expression of interleukin-6 and its receptor results in growth inhibition of MCF-7 breast cancer cells. Anticancer Res. 31:2899–2906. 2011.PubMed/NCBI

15 

Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M and Yao Y: Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther. 141:125–139. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Fizazi K, De Bono JS, Flechon A, Heidenreich A, Voog E, Davis NB, Qi M, Bandekar R, Vermeulen JT, Cornfeld M and Hudes GR: Randomised phase II study of siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer. Eur J Cancer. 48:85–93. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Hunsucker SA, Magarotto V, Kuhn DJ, Kornblau SM, Wang M, Weber DM, Thomas SK, Shah JJ, Voorhees PM, Xie H, et al: Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma. Br J Haematol. 152:579–592. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Hsu CP, Chen YL, Huang CC, Chou CC, Liu CL, Hung CH, Kao TY and Chung YC: Anti-interleukin-6 receptor antibody inhibits the progression in human colon carcinoma cells. Eur J Clin Invest. 41:277–284. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Schneider MR, Hoeflich A, Fischer JR, Wolf E, Sordat B and Lahm H: Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. Cancer Lett. 151:31–38. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Yilmaz S and Simsek I: Early intervention in the treatment of rheumatoid arthritis: focus on tocilizumab. Ther Clin Risk Manag. 9:403–408. 2013.PubMed/NCBI

21 

Oldfield V, Dhillon S and Plosker GL: Tocilizumab: a review of its use in the management of rheumatoid arthritis. Drugs. 69:609–632. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Klein B, Wijdenes J, Zhang XG, Jourdan M, Boiron JM, Brochier J, Liautard J, Merlin M, Clement C, Morel-Fournier B, et al: Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood. 78:1198–1204. 1991.PubMed/NCBI

23 

Sato K, Tsuchiya M, Saldanha J, Koishihara Y, Ohsugi Y, Kishimoto T and Bendig MM: Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth. Cancer Res. 53:851–856. 1993.PubMed/NCBI

24 

Stärkel P, Charette N, Borbath I, Schneider-Merck T, De Saeger C, Abarca J, Leclercq I and Horsmans Y: Ras inhibition in hepatocarcinoma by S-trans-trans-farnesylthiosalicyclic acid: association of its tumor preventive effect with cell proliferation, cell cycle events and angiogenesis. Mol Carcinog. 51:816–825. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Sorriento D, Illario M, Finelli R and Iaccarino G: To NFκB or not to NFκB: The Dilemma on How to Inhibit a Cancer Cell Fate Regulator. Transl Med UniSa. 4:73–85. 2012.PubMed/NCBI

26 

Chang TP and Vancurova I: NFκB function and regulation in cutaneous T-cell lymphoma. Am J Cancer Res. 3:433–445. 2013.PubMed/NCBI

27 

Martin AG: NFκB anti-apoptotic or pro-apoptotic, maybe both. Cell Cycle. 9:3131–3132. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Viatour P, Merville MP, Bours V and Chariot A: Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci. 30:43–52. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kim NH, Kim SK, Kim DS, Zhang D, Park JA, Yi H, Kim JS and Shin HC: Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells. Oncol Lett 9: 2283-2288, 2015.
APA
Kim, N., Kim, S., Kim, D., Zhang, D., Park, J., Yi, H. ... Shin, H. (2015). Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells. Oncology Letters, 9, 2283-2288. https://doi.org/10.3892/ol.2015.3019
MLA
Kim, N., Kim, S., Kim, D., Zhang, D., Park, J., Yi, H., Kim, J., Shin, H."Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells". Oncology Letters 9.5 (2015): 2283-2288.
Chicago
Kim, N., Kim, S., Kim, D., Zhang, D., Park, J., Yi, H., Kim, J., Shin, H."Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells". Oncology Letters 9, no. 5 (2015): 2283-2288. https://doi.org/10.3892/ol.2015.3019
Copy and paste a formatted citation
x
Spandidos Publications style
Kim NH, Kim SK, Kim DS, Zhang D, Park JA, Yi H, Kim JS and Shin HC: Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells. Oncol Lett 9: 2283-2288, 2015.
APA
Kim, N., Kim, S., Kim, D., Zhang, D., Park, J., Yi, H. ... Shin, H. (2015). Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells. Oncology Letters, 9, 2283-2288. https://doi.org/10.3892/ol.2015.3019
MLA
Kim, N., Kim, S., Kim, D., Zhang, D., Park, J., Yi, H., Kim, J., Shin, H."Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells". Oncology Letters 9.5 (2015): 2283-2288.
Chicago
Kim, N., Kim, S., Kim, D., Zhang, D., Park, J., Yi, H., Kim, J., Shin, H."Anti‑proliferative action of IL‑6R-targeted antibody tocilizumab for non-small cell lung cancer cells". Oncology Letters 9, no. 5 (2015): 2283-2288. https://doi.org/10.3892/ol.2015.3019
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