Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Tocilizumab Exerts Anti-tumor Effects on Proliferation, Invasiveness, ERK 1/2 and STAT3 Signaling Transduction in Colorectal Carcinoma Cell Xenografts Corresponding to Expression Levels of IL-6 Receptors

Version 1 : Received: 24 November 2023 / Approved: 28 November 2023 / Online: 28 November 2023 (03:43:13 CET)

A peer-reviewed article of this Preprint also exists.

Chung, Y.-C.; Chen, S.-J.; Huang, C.-C.; Liu, W.-C.; Lai, M.-T.; Kao, T.-Y.; Yang, W.-S.; Yang, C.-H.; Hsu, C.-P.; Chang, J.-F. Tocilizumab Exerts Anti-Tumor Effects on Colorectal Carcinoma Cell Xenografts Corresponding to Expression Levels of Interleukin-6 Receptor. Pharmaceuticals 2024, 17, 127. Chung, Y.-C.; Chen, S.-J.; Huang, C.-C.; Liu, W.-C.; Lai, M.-T.; Kao, T.-Y.; Yang, W.-S.; Yang, C.-H.; Hsu, C.-P.; Chang, J.-F. Tocilizumab Exerts Anti-Tumor Effects on Colorectal Carcinoma Cell Xenografts Corresponding to Expression Levels of Interleukin-6 Receptor. Pharmaceuticals 2024, 17, 127.

Abstract

Tocilizumab against interleukin-6 receptor (IL-6R) has been demonstrated to inhibit the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of Tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels re-mains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as our human CRC xenograft models with anti-IL-6R antibody (Tocilizumab) therapy. IL-6R expression levels, the histology of CRC growth/ invasiveness and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels exerted better responsiveness in Tocilizumab therapy than the treated HT-29 group. Likewise, therapeutic effects of Tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, the invasiveness with MMP-9 proteinase expressions, ERK 1/2 and STAT3 signaling transduction in SW480 treatment group were superior to HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of Tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, Tocilizumab may serve as a targeted and promising anti-CRC therapy.

Keywords

Interleukin-6 receptor; colorectal carcinoma; xenograft; Tocilizumab; Ki-67; ERK 1/2; STAT3

Subject

Biology and Life Sciences, Life Sciences

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