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Oncotarget ; 6(15): 13671-87, 2015 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-25909174

RESUMO

Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by KrasG12D or EGFRL858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endoplasmic reticulum (ER) stress. Blockage of ER stress in SYK023-treated cells inhibited SYK023-induced apoptosis. In addition, we found that the expression of cell cycle-related genes, including cyclin A2, B1, D3, CDC25a, and CDC25b decreased but, while those of p15INK4b, p16INK4a, and p21CIP1 increased following SYK023 treatment. Finally, low doses of SYK023 significantly decreased lung cancer metastasis in vitro and in vivo. Expression of several genes related to cell migration, including synaptopodin, were downregulated by SYK023, thereby impairing F-actin polymerization and metastasis. Therefore, SYK023 may be a potentially therapeutic treatment for metastatic lung cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Triterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Camundongos Transgênicos , Metástase Neoplásica , Triterpenos Pentacíclicos , Prognóstico , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto , Ácido Betulínico
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