Anti-esophageal cancer activity of JNJ-26481585 and its molecular mechanism / 中国药理学通报
Chinese Pharmacological Bulletin
;
(12): 561-565, 2019.
Article
in Chinese
| WPRIM
| ID: wpr-857377
ABSTRACT
Aim:
To study the anti-esophageal cancer activity of a pan-HDAC inhibitor JNJ-26481585 and its molecular mechanism.Methods:
Esophageal cancer cell line TE-1 was treated with vehicle control or serial dilutions of JNJ-26481585, and then MTT and colony formation assay, EdU incorporayion assay, and flow cytometry were performed to detect cell viability, cell proliferation, cell cycle and apoptosis, respectively. The anti-metastasis activity of JNJ-26481585 was assessed according to wound healing assay and Transwell invasion assay. Additionally, Western blot was performed to detect the influence of JNJ-26481585 on the growth-related signaling pathways of esophageal cancer.Results:
JNJ-26481585 effectively inhibited cellular viability and proliferation of TE-1 cells, as well as induced G2/M phase arrest and apoptosis even at low treatment concentrations. Meanwhile, it also had the ability to suppress the migration and invasion of TE-1 cells. The results of Western blotting indicated that JNJ-26481585 treatment could significantly up-regulate the expression level of P21 protein in TE-1 cells, and inhibit the phosphorylation of Akt and ERK, the pivotal proteins of PI3K/mT0R and MAPK pathways, respectively.Conclusions:
JNJ-26481585 exerts its anti-esophageal cancer effects through multiple molecular mechanisms, including up-regulation of cell cycle inhibitor P21 and blockade of Akt/mTOR and ERK signaling cascades.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Chinese Pharmacological Bulletin
Year:
2019
Type:
Article
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