Influence of ciglitazone on A549 cells growth in vitro and in vivo and mechanism.
The effect and mechanism of the ciglitazone on lung cancer cells A549 growth in vitro and in vivo were studied. Various concentrations of ciglitazone were added to the cultured A549 line, and the proliferation and differentiation of A549 cells were examined by MTT and cytometry analysis. A549 cells (1 x 10(6)/mouse) were inoculated subcutaneously into 20 nude mice, which were randomly divided into two groups: the control group, the ciglitazone treated group. The weights of subcutaneous tumors were measured. The expression of cyclin D1 and P21 in the lung was detected by immohistochemistry and Western blot respectively. The results showed that the proliferation of A549 was inhibited significantly by ciglitazone in a dose- and time-dependent manner. There were more cells arrested in G1 /G0 phase and the expression of PPARgamma was markedly up-regulated in ciglitazone-treated group. Direct injection of ciglitazone into A549-induced tumors could suppress tumor growth in nude mice and the growth inhibitory rate was 36%. The expression of cyclin D1 was decreased and P21 increased significantly in ciglitazone-treated group as compared with control group. It was concluded that ciglitazone could inhibit A549 proliferation dose-dependently and time-dependently and induce differentiation, which might be related to the modulation of cell cycle interfered by PPARgamma.
Zhang
Wanguang
W
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhang
Huilan
H
Xing
Lihua
L
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D011897:Random Allocation; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D047495:PPAR gamma; D045162:Thiazolidinediones; D019938:Cyclin D1; C039671:ciglitazone