NVP-BEZ235 inhibits thyroid cancer growth by p53- dependent/independent p21 upregulation

Autor: Qi Yang, Meiju Ji, Pu Chen, Rongrong Cui, Banjun Ruan, Peng Hou, Wei Liu, Yu Li
Rok vydání: 2020
Předmět:
p53
rho GTP-Binding Proteins
Cell cycle checkpoint
Blotting
Western
Mutant
Fluorescent Antibody Technique
Mice
Nude
Real-Time Polymerase Chain Reaction
Applied Microbiology and Biotechnology
Thyroid cancer
Cell cycle arrest
Mice
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
medicine
Animals
Thyroid Neoplasms
Protein Kinase Inhibitors
Molecular Biology
Ecology
Evolution
Behavior and Systematics
PI3K/AKT/mTOR pathway
030304 developmental biology
Mice
Inbred BALB C
0303 health sciences
p21
business.industry
Imidazoles
Wild type
Cell Cycle Checkpoints
Cell Biology
Flow Cytometry
medicine.disease
Immunohistochemistry
Xenograft Model Antitumor Assays
NVP-BEZ235
Cancer cell
Quinolines
Cancer research
Female
PI3K/Akt/mTOR
Tumor Suppressor Protein p53
business
G1 phase
Research Paper
Signal Transduction
Developmental Biology
Zdroj: International Journal of Biological Sciences
ISSN: 1449-2288
DOI: 10.7150/ijbs.37592
Popis: NVP-BEZ235 is a novel dual PI3K/mTOR inhibitor, currently in phase 1/2 clinical trials, exhibiting clinical efficiency in treatment of numerous malignancies including thyroid cancer. Cancer cells harboring mutant p53 was widely reported to be blunt to pharmaceutical therapies. However, whether this genotype dependent effect also presents in thyroid cancer when treated with NVP-BEZ235 remains unknown. Therefore, in this study, the tumor suppressing effects of NVP-BEZ235 in thyroid cancer cell lines and in-vivo xenograft mouse model harboring different p53 status were examined. The antitumor effects were confirmed in p53 mutant thyroid cancer cells, though less prominent than p53 wild type cells. And for the p53 mutant cells, p53-independent upregulation of p21 plays a critical role in their response to NVP-BEZ235. Moreover, GSK3β/β-catenin signaling inhibition was implicated in the p21-mediated G0/G1 cell cycle arrest in both p53 wild type and mutant thyroid cancer cells treated with NVP-BEZ235.
Databáze: OpenAIRE
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