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Métodos Terapêuticos e Terapias MTCI
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J Pharm Pharmacol ; 73(1): 98-109, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33791802

RESUMO

OBJECTIVES: To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance. METHODS: TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo. KEY FINDINGS: The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo. CONCLUSIONS: PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Células Escamosas , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Naftoquinonas/farmacologia , Extratos Vegetais/uso terapêutico , Neoplasias da Língua , Língua/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Autofagia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Naftoquinonas/uso terapêutico , Fitoterapia , Extratos Vegetais/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Língua/metabolismo , Língua/patologia , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia
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