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PX-12 Inhibits the Growth of Hepatocelluar Carcinoma by Inducing S-phase Arrest, ROS-dependent Apoptosis and Enhances 5-FU Cytotoxicity

Guang-Zhen Li, Hui-Fang Liang, Bo Liao, Lei Zhang, Ya-An Ni, Hong-Hao Zhou, Er-Lei Zhang, Bi-Xiang Zhang, Xiao-Ping Chen

Am J Transl Res. 2015 Sep 15;7(9):1528-40.

PMID: 26550453

Abstract:

Background:
1-methylpropyl 2-imidazolyl disulfide (PX-12), a thioredoxin 1 (Trx1) inhibitor, has been investigated in a number of ancers, but its effectiveness in the treatment of hepatocellular carcinoma (HCC) has not been reported. PX-12 has generated considerable interest in its use in a variety of solid tumors, yet most studies have confined their interests to using PX-12 as a single agent. The aim of this study is to investigate whether PX-12 inhibits cell growth and has a synergistic anti-tumor effect in combination with 5-fluorouracil (5-FU) in HCC.
Methods:
Cells were treated with different concentrations of PX-12 and 5-FU. Cell viability assays, colony formation assay, cell cycle assay, reactive oxygen species (ROS) assay, apoptosis analysis, western blot assay, immunohistochemistry and xenograft tumorigenicity assay were performed.
Results:
Treatment with PX-12 inhibited cell growth, induced S-phase arrest, and increased ROS levels. PX-12-induced apoptosis and inhibition of colony formation were associated with the generation of ROS, and inhibition of ROS attenuated PX-12-induced apoptosis and inhibition of colony formation. Treatment with PX-12 increased the expression of bax and reduced the expression of bcl-2, indicating that PX-12-mediated apoptosis is mitochondria-dependent. PX-12 also exerted a synergistic effect with 5-FU tosignificantly suppress tumorigenicity both in vitro and in vivo. Inhibition of ROS accumulation reduced the synergistic effect of PX-12 and 5-FU.
Conclusions:
PX-12 has anti-tumor activity and a synergistic effect in combination with 5-FU in HCC. Treatment with PX-12 alone or in combination with 5-FU may have clinical use in the treatment of HCC and other cancers.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP141400580 PX 12 PX 12 141400-58-0 Price
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