Buformin suppresses osteosarcoma via targeting AMPK signaling pathway

Background: Buformin has been reported to be a powerful anticancer drug by activating the AMPK signal. Herein, we aimed to investigate the effects of buformin on osteosarcoma. Material and methods: Cellular proliferative abilities were determined by cell counting kit-8 and colony formation assays. Cellular invasion was investigated using a transwell system. Cell cycle was examined by flow cytometry. Western blot was performed to measure the expression of key proteins. Synergistic effects of buformin and cisplatin were validated in seven fresh osteosarcoma tissues. Results: Buformin suppressed the growth of U-2 OS cells in a dose-dependent manner (IC50 = 69.1 µM). Moreover, buformin induced cell cycle arrest (P < 0.001) and impaired cellular invasion (P = 0.038). Phosphorylation of AMPK was upregulated by buformin, while phosphorylation of S6, cyclin D1, and MMP9 were significantly downregulated. In addition, buformin notably induced accumulation of reactive oxygen species and lactate and eventually decreased ATP production. In both U-2 OS cells and the primary cultured osteosarcoma tissues, buformin increased tumor sensitivity to cisplatin. Conclusions: Buformin could suppress tumor growth and invasion of osteosarcoma through directly targeting the AMPK signaling pathway. Moreover, buformin inhibited the abnormal metabolism and notably increased the cytotoxicity of cisplatin, and therefore represents a new potential treatment option for osteosarcoma.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Buformin suppresses osteosarcoma via targeting AMPK signaling pathway ; volume:15 ; number:1 ; year:2020 ; pages:409-417 ; extent:9
Open life sciences ; 15, Heft 1 (2020), 409-417 (gesamt 9)

Urheber
Ding, Yan
Lv, Shiqiao
Li, Guangrun
Cui, Jinpeng
Chen, Yunzhen

DOI
10.1515/biol-2020-0041
URN
urn:nbn:de:101:1-2409201746428.389892337052
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:20 MESZ

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Beteiligte

  • Ding, Yan
  • Lv, Shiqiao
  • Li, Guangrun
  • Cui, Jinpeng
  • Chen, Yunzhen

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