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Dual STAT‑3 and IL‑6R inhibition with stattic and tocilizumab decreases migration, invasion and proliferation of prostate cancer cells by targeting the IL‑6/IL‑6R/STAT‑3 axis

  • Authors:
    • Anibal Méndez‑Clemente
    • Alejandro Bravo‑Cuellar
    • Salvador González‑Ochoa
    • Maria Santiago‑Mercado
    • Luis Palafox‑Mariscal
    • Luis Jave‑Suárez
    • Fabiola Solorzano‑Ibarra
    • Maria Villaseñor‑García
    • Pablo Ortiz‑Lazareno
    • Georgina Hernández‑Flores

  • View Affiliations

  • Published online on: June 14, 2022     https://doi.org/10.3892/or.2022.8349
  • Article Number: 138

  • Copyright : © Méndez‑Clemente et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Prostate cancer (PCa) is a key public health problem worldwide; at diagnosis, a high percentage of patients exhibit tumor cell invasion of adjacent tissue. STAT‑3, IL‑6 receptor (R) and IL‑6 serum levels are associated with enhanced PCa migratory, invasive, clonogenic and metastatic ability. Inhibiting the STAT‑3 pathway at different levels (cytokines, receptors, and kinases) exhibits relative success in cancer. The present study investigated the effect of Stattic (Stt) + Tocilizumab (Tcz) on proliferative, clonogenic, migratory and invasive ability of human metastatic PCa (assessed by colony formation, wound healing and migration assay). RWPE‑1 (epithelial prostate immortalized cells), 22Rv1 (Tumor cells), LNCaP (Metastatic cells) and DU‑145 (metastatic, castration‑resistant prostate cells) cells were used in vitro to evaluate levels of cytokines, chemokines, growth factors (Cytometric Bead Array), STAT‑3, phosphorylated STAT‑3 (In‑Cell Western), IL‑6R, vimentin and epithelial (E‑) cadherin (Western Blot). The effect of inhibition of STAT‑3 (expressed constitutively in DU‑145 cells) with Stt and/or Tcz on expression levels of vimentin, VEGF, and E‑cadherin, as well as proliferative, clonogenic, migratory and invasive capacity of metastatic PCa cells was assessed. The expression levels of IL‑6, C‑X‑C chemokine ligand 8, VEGF and vimentin, as well as proliferation and migration, were increased in metastatic PCa cells. Treatment with Stt or Tcz decreased vimentin and VEGF and increased E‑cadherin expression levels and inhibited proliferative, clonogenic, migratory and invasive capacity of DU‑145 cells; addition of IL‑6 decreased this inhibitory effect. However, Stt + Tcz maintained inhibition even in the present of high concentrations of IL‑6. Stt + Tcz decreased expression of vimentin and VEGF and inhibited the proliferative, clonogenic, migratory and invasive capacity of metastatic PCa cells. To the best of our knowledge, the present study is the first to combine Stt, a STAT‑3 inhibitor, with Tcz, an antibody against IL‑6R, to target tumor cells.
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August-2022
Volume 48 Issue 2

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Spandidos Publications style
Méndez‑Clemente A, Bravo‑Cuellar A, González‑Ochoa S, Santiago‑Mercado M, Palafox‑Mariscal L, Jave‑Suárez L, Solorzano‑Ibarra F, Villaseñor‑García M, Ortiz‑Lazareno P, Hernández‑Flores G, Hernández‑Flores G, et al: Dual STAT‑3 and IL‑6R inhibition with stattic and tocilizumab decreases migration, invasion and proliferation of prostate cancer cells by targeting the IL‑6/IL‑6R/STAT‑3 axis. Oncol Rep 48: 138, 2022
APA
Méndez‑Clemente, A., Bravo‑Cuellar, A., González‑Ochoa, S., Santiago‑Mercado, M., Palafox‑Mariscal, L., Jave‑Suárez, L. ... Hernández‑Flores, G. (2022). Dual STAT‑3 and IL‑6R inhibition with stattic and tocilizumab decreases migration, invasion and proliferation of prostate cancer cells by targeting the IL‑6/IL‑6R/STAT‑3 axis. Oncology Reports, 48, 138. https://doi.org/10.3892/or.2022.8349
MLA
Méndez‑Clemente, A., Bravo‑Cuellar, A., González‑Ochoa, S., Santiago‑Mercado, M., Palafox‑Mariscal, L., Jave‑Suárez, L., Solorzano‑Ibarra, F., Villaseñor‑García, M., Ortiz‑Lazareno, P., Hernández‑Flores, G."Dual STAT‑3 and IL‑6R inhibition with stattic and tocilizumab decreases migration, invasion and proliferation of prostate cancer cells by targeting the IL‑6/IL‑6R/STAT‑3 axis". Oncology Reports 48.2 (2022): 138.
Chicago
Méndez‑Clemente, A., Bravo‑Cuellar, A., González‑Ochoa, S., Santiago‑Mercado, M., Palafox‑Mariscal, L., Jave‑Suárez, L., Solorzano‑Ibarra, F., Villaseñor‑García, M., Ortiz‑Lazareno, P., Hernández‑Flores, G."Dual STAT‑3 and IL‑6R inhibition with stattic and tocilizumab decreases migration, invasion and proliferation of prostate cancer cells by targeting the IL‑6/IL‑6R/STAT‑3 axis". Oncology Reports 48, no. 2 (2022): 138. https://doi.org/10.3892/or.2022.8349