Titanium dioxide nanoparticles induce endoplasmic reticulum stress-mediated apoptotic cell death in liver cancer cells

Autor: Zuguang Wu, Guoan Xiang, Jinqian Zhang, Xiaopeng Duan, Jingliang He, Ke He, Zhiwang Li, Bowei Li, Rui Huang
Rok vydání: 2020
Předmět:
Zdroj: The Journal of International Medical Research
Journal of International Medical Research, Vol 48 (2020)
ISSN: 1473-2300
0300-0605
DOI: 10.1177/0300060520903652
Popis: Objective Titanium oxide (TiO2) acts as a photosensitizer in photodynamic therapy by mediating reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress. This study aimed to investigate the effect of TiO2 on ER stress in liver cancer cells. Methods Normal human liver and human hepatocarcinoma cell lines were incubated with various concentrations of TiO2 nanotubes for 48 hours. Cell growth, apoptosis, cell cycle, and cellular ROS were detected. Expression levels of ER stress sensors (PERK and ATF6) and Bax were evaluated by western blot. The effect of TiO2 on liver cancer growth was also investigated in mice in vivo. Results TiO2 inhibited cell growth, increased apoptosis and cellular ROS levels, and arrested the cell cycle in G1 stage in liver cancer cells. TiO2 also increased PERK, ATF6, and Bax expression levels in liver cancer cells in dose-dependent manners. TiO2 had no significant effect on cell growth, apoptosis, ROS level, cell cycle distribution, or PERK, ATF6, or Bax expression in normal liver cells. TiO2 administration reduced tumor volume and increased PERK, Bax, and ATF6 expression levels in tumor tissues in vivo. Conclusions TiO2 nanoparticles increased ROS-induced ER stress and activated the PERK/ATF6/Bax axis in liver cancer cells in vitro and in vivo.
Databáze: OpenAIRE