[Effects of 17-AAG on the proliferation and apoptosis of human lung cancer A549 and H446 cells].
OBJECTIVE
To observe the effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) on the apoptosis of human lung cancer cell lines A549 and H446, and to investigate the potential mechanisms.


METHODS
Proliferation inhibition and apoptosis assays, and the cell cycles were detected by MTT and flow cytometry respectively. Western blot was used to determine the expression level of proteins such as Hsp90, Hsp70, AKt, Her-2, Bcl-2 and Bax.


RESULTS
After treated with 17-AAG, the proliferation of both A549 and H446 cells was inhibited significantly in a dose-dependent manner; as the concentration of 17-AAG was from 50 to 500 nmol/L, the IC₅₀ values to A549 and H446 cell lines were (222 ± 13) nmol/L and (189 ± 7) nmol/L respectively at 48 h. Cell cycle assays showed that 17-AAG was able to arrest cell cycles of A549 and H446 cell lines at the G₂/M phase. Apoptosis assay showed that 17-AAG was capable of inducing apoptosis in A549 and H446 cell lines. After treated with 17-AAG for 48 h, there were significant differences between the 400 nmol/L groups(46.3% for A549 cell line and 56.9% for H446 cell line) and the control group (11.9% for A549 cell line and 6.9% for H446 cell line, P < 0.01). Western blot results showed that the relative proteins of the Hsp90 signal pathway in both A549 and H446 cell lines underwent similar changes after 17-AAG treatment: Akt and Her-2 decreased significantly while the expression of Hsp70 increased. Meanwhile, the expression of Bcl-2 decreased but that of Bax increased, indicating that 17-AAG was able to promote apoptosis mode in A549 and H446 cells.


CONCLUSIONS
17-AAG can regulate the expression level of apoptosis-related proteins such as Bax and Bcl-2 by Hsp90 signaling pathway in A549 and H446 cells, and ultimately inhibit cell proliferation and induce apoptosis.
Department of Respiratory Medicine, Central Hospital of Shengli Oilfield, Dongying 257034, China.
Ben
B
Niu
Department of Respiratory Medicine, Central Hospital of Shengli Oilfield, Dongying 257034, China.
Jingshuang
J
Lin
Department of Respiratory Medicine, Central Hospital of Shengli Oilfield, Dongying 257034, China; Email: fengtao1972@163.com.
Tao
T
Feng
D017209:Apoptosis; D016227:Benzoquinones; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D018841:HSP90 Heat-Shock Proteins; D006801:Humans; D047029:Lactams, Macrocyclic; D008175:Lung Neoplasms; D015398:Signal Transduction
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin