Matrine reduces proliferation of human lung cancer cells by inducing apoptosis and changing miRNA expression profiles.
Matrine, a main active component extracted from dry roots of Sophora flavecens , has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and time- dependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China E-mail : xdxie@lzu.edu.cn.
Yong-Qi
YQ
Liu
Yi
Y
Li
Jie
J
Qin
Qian
Q
Wang
Ya-Li
YL
She
Ya-Li
YL
Luo
Jian-Xin
JX
He
Jing-Ya
JY
Li
Xiao-Dong
XD
Xie
D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D056284:Histone Deacetylase 1 / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011807:Quinolizines / Q000494:pharmacology*; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics; D000093842:Matrines
D000470:Alkaloids; D000970:Antineoplastic Agents; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D011807:Quinolizines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D000093842:Matrines