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Invest New Drugs ; 39(2): 377-385, 2021 04.
Article in English | MEDLINE | ID: mdl-32989643

ABSTRACT

Purpose Our study aimed to investigate the antitumor effects of rAj-Tspin on BEL-7402 hepatocellular carcinoma cells and to explore the underlying mechanism. Method For the in vivo experiment, BEL-7402 cells were inoculated subcutaneously into the axilla of nude mice to generate a BEL-7402 cell-bearing model, and model mice were then treated with different doses of rAj-Tspin. A CCK-8 assay was used to evaluate the in vitro viability of BEL-7402 and LO2 cells after treatment with different concentrations of rAj-Tspin. The effects of rAj-Tspin on BEL-7402 cell apoptosis, migration and invasion were evaluated by AO/EB and Hoechst fluorescent staining and by scratch and Transwell assays, and the tumor-suppressive mechanism of rAj-Tspin was explored by Western blotting. Results rAj-Tspin suppressed the proliferation of BEL-7402 cells with an IC50 of 0.89 µM. The results of both microscopic analysis and Western blotting suggested that rAj-Tspin induced the apoptosis of BEL-7402 cells through a mitochondria-dependent pathway. Furthermore, rAj-Tspin disrupted EMT; this disruption ultimately caused BEL-7402 cells to lose their shape and decreased their migration and invasion. Moreover, rAj-Tspin might inhibit the proliferation and metastasis of BEL-7402 cells through the ITGB1-FAK-AKT pathway. Conclusion rAj-Tspin exerts an antitumor effect through the ITGB1-FAK-Akt signaling pathway and exhibits low toxicity at an effective dose.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Stichopus , Animals , Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Focal Adhesion Kinase 1/drug effects , Integrin beta1/drug effects , Liver Neoplasms/pathology , Male , Marine Toxins/pharmacology , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness/prevention & control , Peptides/pharmacology , Proto-Oncogene Proteins c-akt/drug effects , Signal Transduction/drug effects , Xenograft Model Antitumor Assays
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