[Ciglitazone inhibits growth of lung cancer cells A549 in vitro and in vivo: an experimental study].
OBJECTIVE
To study the inhibitory effects of ciglitazone, a synthetic ligand of peroxisome proliferator-activated receptors (PPAR), on human lung cancer growth in vitro and in vivo and its mechanisms.


METHODS
Human lung cancer A549 cells cultured in vitro were treated with different concentrations of ciglitazone. The proliferative activity and cell cycle of A549 cells were determined by MTT assay and flow cytometry. Expression of PPARgamma protein was detected by Western blot. A549 cells (1 x 10(6) cells/nude mouse) were inoculated subcutaneously into nude mice, which were randomly divided into two groups, 10 in each: control group (group A) and ciglitazone treated group (group B). When the tumors grew to a size with diameter around 1 cm, ciglitazone 100 microl (100 micromol/L) was intratumorally injected every other day in group B mice. A total of 15 injections were given. Mice in group A were similarly treated with normal saline. One month later, tumors were excised and weighed. Expression of cyclin D1 and p21 protein were detected by immunohistochemistry and Western blot.


RESULTS
Growth of A549 cells was significantly inhibited in group B in a dose-dependent and time-dependent fashion as compared with that in group A. Most of the ciglitazone-treated cells arrested in G(1)/G(0) phase and the expression of PPARgamma protein was markedly up-regulated. The tumor weights in group A was (2.79 +/- 0.33) g and that in group B was (1.51 +/- 0.40) g, with an inhibition rate of 47.0%. The expression level of cyclin D1 in group A was significantly higher than that in group B, while the expression level of p21 protein in group A was significantly lower than that in group B.


CONCLUSIONS
Ciglitazone can effectively inhibit the growth of human lung cancer A549 and induce its differentiation by cell cycle arrest via PPARgamma activation.
Zhang
Hui-lan
HL
Department of Respiratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. huilanz_76@hotmail.com
Zhang
Zhen-xiang
ZX
Xu
Yong-jian
YJ
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047495:PPAR gamma / Q000378:metabolism*; D011897:Random Allocation; D016192:Resting Phase, Cell Cycle; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D050759:Cyclin-Dependent Kinase Inhibitor p21; D047495:PPAR gamma; D045162:Thiazolidinediones; D019938:Cyclin D1; C039671:ciglitazone