TY - JOUR
T1 - Sinoporphyrin sodium based sonodynamic therapy induces anti-tumor effects in hepatocellular carcinoma and activates p53/caspase 3 axis
AU - Li, Enze
AU - Sun, Yi
AU - Lv, Guixiang
AU - Li, Yongning
AU - Zhang, Zhiguo
AU - Hu, Z.
AU - Cao, W.
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/8
Y1 - 2019/8
N2 - Sonodynamic therapy (SDT) is a noninvasive therapeutic method via the activation of certain chemical sensitizers using low intensity ultrasound. In this work, we evaluated the antitumor effect of sinoporphyrin sodium (DVDMS) mediated SDT (DVDMS-SDT) on Hepatocellular carcinoma (HCC) cell lines both in vitro and in vivo. The results indicated that DVDMS-SDT was significantly more efficacious than PpIX-SDT in treating hepatocellular cell line Hep-G2. DVDMS-SDT also increased the ratio of cells in the G2/M phase and decreased the CDK1 and Cyclin B1 protein level. DVDMS-SDT markedly increased intracellular reactive oxygen species (ROS) in vitro. The increased ROS production up-regulated the expression of p53 and Bax, and down-regulated Bcl-2 expression, which led to the activation of caspase-3, ultimately initiated cell apoptosis. These effects could be partially reversed by the ROS scavenger N-acetylcysteine (NAC). In vivo experiments revealed that the DVDMS-SDT resulted in an effective inhibition of tumor growth and prolonged the survival time of tumor-bearing mice. More importantly, no obvious signs of side effects were observed. These results suggested that DVDMS-SDT is very effective in treating Hepatocellular carcinoma without side effects. The primary mechanism of SDT is due to the increased ROS activated the p53/Caspase 3 axis of apoptosis.
AB - Sonodynamic therapy (SDT) is a noninvasive therapeutic method via the activation of certain chemical sensitizers using low intensity ultrasound. In this work, we evaluated the antitumor effect of sinoporphyrin sodium (DVDMS) mediated SDT (DVDMS-SDT) on Hepatocellular carcinoma (HCC) cell lines both in vitro and in vivo. The results indicated that DVDMS-SDT was significantly more efficacious than PpIX-SDT in treating hepatocellular cell line Hep-G2. DVDMS-SDT also increased the ratio of cells in the G2/M phase and decreased the CDK1 and Cyclin B1 protein level. DVDMS-SDT markedly increased intracellular reactive oxygen species (ROS) in vitro. The increased ROS production up-regulated the expression of p53 and Bax, and down-regulated Bcl-2 expression, which led to the activation of caspase-3, ultimately initiated cell apoptosis. These effects could be partially reversed by the ROS scavenger N-acetylcysteine (NAC). In vivo experiments revealed that the DVDMS-SDT resulted in an effective inhibition of tumor growth and prolonged the survival time of tumor-bearing mice. More importantly, no obvious signs of side effects were observed. These results suggested that DVDMS-SDT is very effective in treating Hepatocellular carcinoma without side effects. The primary mechanism of SDT is due to the increased ROS activated the p53/Caspase 3 axis of apoptosis.
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U2 - 10.1016/j.biocel.2019.01.009
DO - 10.1016/j.biocel.2019.01.009
M3 - Article
C2 - 30660690
AN - SCOPUS:85060843817
SN - 1357-2725
VL - 113
SP - 104
EP - 114
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
ER -