Centre for Kidney Disease Research, The University of Queensland, Translational Research Institute, Brisbane, Australia; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
Centre for Kidney Disease Research, The University of Queensland, Translational Research Institute, Brisbane, Australia.
Biochem Biophys Res Commun. 2022 Jan 1;586:42-48. doi: 10.1016/j.bbrc.2021.11.069. Epub 2021 Nov 20.
Sunitinib is one of the first-line multi-tyrosine kinase inhibitors for metastatic renal cell carcinoma, and resistance to sunitinib continues to be a limiting factor for the successful treatment. As interleukin-6 (IL-6) is overexpressed in sunitinib-resistant cells, the purpose of this study was to explore the potential of IL-6 inhibition with tocilizumab, an IL-6 receptor inhibitor, to overcome resistance. In vitro, two sunitinib-resistant renal cell carcinoma cell lines (Caki-1 and SN12K1) were treated with tocilizumab. A mouse subcutaneous xenograft model was also used. Cell viability was studied by MTT assay, and apoptosis by morphology and ApopTag. Expression of IL-6, vascular endothelial growth factor (VEGF), and Bcl-2 was analyzed by qPCR. In vitro, tocilizumab induced significant cell death, and reduced the expression of IL-6, VEGF, and Bcl-2 in sunitinib-resistant cells. However, the in vitro findings could not be successfully translated in vivo, as tocilizumab did not decrease the growth of the tumors.
舒尼替尼是转移性肾细胞癌的一线多酪氨酸激酶抑制剂之一，对舒尼替尼的耐药性仍然是成功治疗的限制因素。由于白细胞介素 6（IL-6）在舒尼替尼耐药细胞中过度表达，本研究旨在探讨用白细胞介素 6 受体抑制剂托珠单抗抑制 IL-6 以克服耐药性的潜力。在体外，用托珠单抗处理两种舒尼替尼耐药肾癌细胞系（Caki-1 和 SN12K1）。还使用了小鼠皮下异种移植模型。通过 MTT 测定研究细胞活力，通过形态学和 ApopTag 研究细胞凋亡。通过 qPCR 分析白细胞介素 6、血管内皮生长因子（VEGF）和 Bcl-2 的表达。在体外，托珠单抗诱导明显的细胞死亡，并降低了舒尼替尼耐药细胞中 IL-6、VEGF 和 Bcl-2 的表达。然而，体外的发现无法在体内成功转化，因为托珠单抗并没有减少肿瘤的生长。
