Effect of ZGDHu-1 on proliferation and apoptosis of A549 cells in vitro and antitumor activity in vivo.
- Author:
Yong-Lie ZHOU
1
;
Wei-Xiao HU
;
Ya-Ping LÜ
;
Lian-Nü QIU
;
Wen-Song WANG
;
Zhong-Yu YANG
;
Jian-Dong LIU
;
Guo-Wu RAO
Author Information
1. Central Laboratory, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents;
pharmacology;
Apoptosis;
drug effects;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Dose-Response Relationship, Drug;
Female;
Flow Cytometry;
Heterocyclic Compounds, 1-Ring;
pharmacology;
Humans;
Lung Neoplasms;
metabolism;
pathology;
prevention & control;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Proto-Oncogene Proteins c-bcl-2;
biosynthesis;
genetics;
RNA, Messenger;
biosynthesis;
genetics;
Random Allocation;
Reverse Transcriptase Polymerase Chain Reaction;
Tumor Suppressor Protein p53;
biosynthesis;
genetics;
Xenograft Model Antitumor Assays;
bcl-2-Associated X Protein;
biosynthesis;
genetics
- From:
Acta Pharmaceutica Sinica
2007;42(1):26-34
- CountryChina
- Language:Chinese
-
Abstract:
This study is to explore the mechanism and effect of N, N'-di-(m-methylphenyl)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide (ZGDHu-1) on proliferation and apoptosis of A549 cells in vitro and on A549 xenograft tumor in nude mice. With different concentrations of ZGDHu-1 at different times were used to treat A549 cells in vitro. The proliferation was determined by living cell count, SRB assay and Brdu-ELISA. Cell apoptosis was determined by cell morphology, DNA agarose gel electrophoresis, DNA content, Annexin V/PI and Hoechst 33258 labeling method. The nude mice model of A549 xenograft tumor was established by subcutaneous inoculation. The suppression activity of ZGDHu-1 by intraperitoneal injection on xenograft mice model was detected. The expressions of bcl-2, bax and p53 gene and protein were analyzed by RT-PCR and flow cytometry. ZGDHu-1 can inhibit A549 cell proliferation viability within a certain range of treating time and does, and a majority of A549 cells were arrested in G2-M phase. The A549 cells apoptosis was confirmed by typical cell morphology, DNA fragment, Sub G1 phase, Hoechst 33258 and Annexin V/PI labeling method with a time and dose related manner. When the xenograft tumor mice model were treated with 10, 20 and 40 mg x kg(-1) ZGDHu-1 for 14 days, the tumor growth inhibition rate were 43.7%, 56.9% and 60.0%, respectively. The expression of bax, bax/bcl-2 and p53 gene and protein increased significantly and bcl-2 decreased slightly by the treatment of ZGDHu-1. ZGDHu-1 can significantly suppress the growth of A549 xenograft tumor in vivo and inhibited proliferation by inducing tumor cell apoptosis in vitro. The mechanism may associate with its up-regulation of bax and p53 during the apoptosis process.
