[Mechanisms of G2/M cycle arrest induced by topo IIalpha and II beta inhibitors in H460 cells].
OBJECTIVE
To compare the mechanisms of G(2)/M cycle arrest induced by topo IIalpha and IIbeta inhibitors in H460 cells.


METHODS
The inhibitory effects of XK469, adriamycin and etoposide on H460 cell growth were analyzed by MTT assay. The changes in cell cycle and expressions of cdc2, phos-cdc2 and 14-3-3sigma proteins induced by these 3 topo II inhibitors were detected by flow cytometry and Western blotting, respectively.


RESULTS
Both of the two types of topo II inhibitor resulted in dose-dependent G(2)/M phase arrest and growth inhibition of H460 cells, but XK469 failed to induce 14-3-3sigma protein expression as adriamycin and etoposide did.


CONCLUSIONS
Topo IIalpha and topo IIbeta inhibitors induce growth inhibition of H460 cells possibly through two different mechanisms, namely the 14-3-3sigma-dependent pathway and the 14-3-3sigma-independent pathway, but further functional inhibition test of 14-3-3sigma is needed to confirm this hypothesis.
Ling
Zhao-Hui
ZH
Graduate School, School of Public Health and Tropic Medicine, Southern Medical University, Guangzhou 510515, China. lingzh@fimmu.com
Ding
Zhen-Hua
ZH
D000951:Antigens, Neoplasm; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D016195:G2 Phase; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D011810:Quinoxalines / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D011810:Quinoxalines; D059005:Topoisomerase II Inhibitors; C118180:XK 469; D004250:DNA Topoisomerases, Type II