Salvianolic acid A reverses cisplatin resistance in lung cancer A549 cells by targeting c-met and attenuating Akt/mTOR pathway

Autor: Qing-yong Chen, Li Yan, De-min Jiao, Xiali Tang, Ling Zhu, Jun Chen
Rok vydání: 2017
Předmět:
0301 basic medicine
Lung Neoplasms
endocrine system diseases
Salvia miltiorrhiza
Pharmacology
chemistry.chemical_compound
0302 clinical medicine
Medicine
TOR Serine-Threonine Kinases
Drug Synergism
respiratory system
Proto-Oncogene Proteins c-met
Drug Resistance
Multiple
Up-Regulation
030220 oncology & carcinogenesis
Molecular Medicine
Lung cancer
medicine.drug
Signal Transduction
C-Met
ATP Binding Cassette Transporter
Subfamily B
Antineoplastic Agents
Adenocarcinoma
Alkenes
03 medical and health sciences
Reversal mechanism
Cell Line
Tumor
Humans
Protein kinase B
Cisplatin resistance
PI3K/AKT/mTOR pathway
c-Met
A549 cell
Cisplatin
business.industry
lcsh:RM1-950
Polyphenols
medicine.disease
Salvianolic acid A
respiratory tract diseases
stomatognathic diseases
lcsh:Therapeutics. Pharmacology
030104 developmental biology
chemistry
Cell culture
Drug Resistance
Neoplasm
business
Proto-Oncogene Proteins c-akt
Phytotherapy
Zdroj: Journal of Pharmacological Sciences, Vol 135, Iss 1, Pp 1-7 (2017)
ISSN: 1347-8648
Popis: Drug resistance is one of the leading causes of chemotherapy failure in non-small cell lung cancer (NSCLC) treatment. The purpose of this study was to investigate the role of c-met in human lung cancer cisplatin resistance cell line (A549/DDP) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. In this study, we found that A549/DDP cells exert up-regulation of c-met by activating the Akt/mTOR signaling pathway. We also show that SAA could increase the chemotherapeutic efficacy of cisplatin, suggesting a synergistic effect of SAA and cisplatin. Moreover, we revealed that SAA enhanced sensitivity to cisplatin in A549/DDP cells mainly through suppression of the c-met/AKT/mTOR signaling pathway. Knockdown of c-met revealed similar effects as that of SAA in A549/DDP cells. In addition, SAA effectively prevented multidrug resistance associated protein1 (MDR1) up-regulation in A549/DDP cells. Taken together, our results indicated that SAA suppressed c-met expression and enhanced the sensitivity of lung adenocarcinoma A549 cells to cisplatin through AKT/mTOR signaling pathway.
Databáze: OpenAIRE
Externí odkaz: