rAj-Tspin, a novel recombinant peptide from Apostichopus japonicus , suppresses the proliferation, migration, and invasi
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PRECLINICAL STUDIES
rAj-Tspin, a novel recombinant peptide from Apostichopus japonicus, suppresses the proliferation, migration, and invasion of BEL-7402 cells via a mechanism associated with the ITGB1-FAK-AKT pathway Ping Yu 1 & Rui Wu 2 & Zunchun Zhou 3 & Xin Zhang 1 & Ruoshu Wang 1 & Xueting Wang 1 & Sen Lin 1 & Jihong Wang 2 Li Lv 1
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Received: 29 June 2020 / Accepted: 20 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary 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 rAjTspin. 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 rAjTspin 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 BEL7402 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. Keywords Antitumor . HCC . rAj-Tspin . Apoptosis
Introduction Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide [1–3]. The first step in HCC treatment is surgical resection [4] to reduce the amount of Ping Yu and Rui Wu Co-first authors and these authors contributed equally to this work. * Jihong Wang [email protected] * Li Lv [email protected] 1
Department of Pharmacology, Dalian Medical University, Dalian 116044, Liaoning Province, China
2
School of Life Sciences, Liaoning Normal University, Dalian 116029, Liaoning Province, China
3
Liaoning Ocean and Fisheries Science Research Institute, Dalian 116023, Liaoning Province, China
tumor tissue, and the residual tumor cells are then killed by chemotherapy [5]. However, because prolonged chemotherapy reduces the sensitivity of patients to chemotherapeutic drugs and decreases their bodies’ tolerance to these drugs, the effects of chemotherapy come at a high price. Therefore, the search for chemotherapeutic drugs for primary liver cancer with high efficiency and low toxicity [6, 7] and further discussion of the mechanism underlying the
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