Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF-κB-modulated tumor progression in bladder cancer in vitro and in vivo

Environmental Toxicology
Chih-Hung ChiangFei-Ting Hsu

Abstract

The aim of the present study is to investigate anticancer effect and mechanism of regorafenib in bladder cancer in vitro and in vivo. Human bladder cancer TSGH 8301 cells were treated with regorafenib, NF-κB, AKT, or mitogen-activated protein kinase (MAPK) inhibitors for different time. The changes of cell viability, NF-κB activation, apoptotic signaling transduction, and expression of tumor progression-associated proteins were evaluated with MTT, NF-κB reporter gene assay, flow cytometry, and Western blotting assay. TSGH 8301 tumor bearing mice were established and treated with vehicle (140 μL of 0.1% DMSO) or regorafenib (10 mg/kg/day by gavage) for 15 days. The changes of tumor volume, body weight, NF-κB activation, MAPK activation, and tumor progression-associated proteins (MMP-9, XIAP, VEGF, and Cyclin-D1) after regorafenib treatment were evaluated with digital caliper, digital weight, and ex vivo Western blotting assay. Our results demonstrated NF-κB activation and protein levels of MMP-9, XIAP, VEGF, and Cyclin-D1 were significantly reduced by NF-κB (QNZ), ERK (PD98059), and P38 (SB203580) inhibitors. Regorafenib also significantly induced extrinsic and intrinsic apoptotic signaling transduction in bladder cancer in vitr...Continue Reading

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Citations

Dec 5, 2020·Cancer Management and Research·Dandan QiuZhicheng Cong
Feb 2, 2021·Oxidative Medicine and Cellular Longevity·Chenglin HanXunbo Jin
Jul 29, 2021·Cancer Cell International·Yongwen LuoTao Liu

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Methods Mentioned

BETA
transfection
protein assay
flow cytometry
xenograft

Software Mentioned

Living Image
FlowJo
Image J

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis