Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 558, Issue -, Pages 147-153Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.04.076
Keywords
A438079; Colorectal cancer; Apoptosis; Pyroptosis; Nude mice
Categories
Funding
- National Natural Science Foundation of China [81971459]
Ask authors/readers for more resources
The study revealed that A438079 can inhibit the proliferation, invasion, and migration of CRC cells, and exert therapeutic effects by promoting apoptosis and inhibiting pyroptosis, providing a basis for A438079 as a new drug for CRC.
Background: Our previous study identified elevated expression of the P2X7 receptor (P2X7R) in colorectal cancer (CRC) patients, suggesting the receptor is a target for predicting poor disease prognosis. A438079 is a highly selective P2X7R antagonist, however, no studies have identified A438079 effects and mechanisms toward the biological behavior of CRC cells, and its therapeutic in vivo potential in CRC nude mice. Methods: The CRC cell lines, HCT-116 and SW620 were treated with 10 mM A438079, after which proliferation, migration, invasion, and apoptosis were assessed. SW620 cell xenografted BALB/c nude male mice were randomly divided into control, 5-FU, and A438079 groups. Mouse weight and tumor dimensions were also measured every two days. Furthermore, the expression of apoptosis related indicators (P2X7R, Bcl-2, Bax, caspase9, cleaved caspase9, caspase3, and cleaved caspase3) and pyroptosis related indicators (NLRP3, ASC, cleaved caspase1, and interleukin (IL) -b) were investigated in vitro and in vivo. Results: A438079 inhibited HCT-116 and SW620 cell proliferation, invasion and migration, and inhibited the growth of CRC xenografts in nude mice. A438079 promoted apoptosis via the Bcl-2/caspase9/ caspase3 pathway and inhibited pyroptosis through the NLRP3/caspase1 pathway by inhibiting P2X7R in vitro and in vivo. Conclusions: We preliminarily confirmed the therapeutic potential of A438079 toward CRC, and we provide a sound theoretical basis for A438079 as a new drug for the clinical treatment of CRC. (c) 2021 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available