ABSTRACT
OBJECTIVE To study the effect of different concentrations of 17-AAG and EGCG monotherapy or in combination on the induced apoptosis in human nasopharyngeal carcinoma, and to explore new molecular targets for the treatment of nasopharyngeal carcinoma. METHODS MTT colorimetric method and fluorescent staining were used to detect the change of CNE proliferation inhibition rate and cell morphology. And furthermore, the expression level of Bcl-2, Bax, Caspase-3 were detected by RT-PCR. RESULTS 1. 17-AAG or EGCG alone had inhibitory effect on the human nasopharyngeal carcinoma CNE cells at 24 h, 48h and 72 h, and it was related with time and dose(P<0.01). The inhibition effect of combination of 17-AAG and EGCG was significantly increased,which was time and dose dependent(P<0.01). 2. RT-PCR was used to detect the mRNA expression level of Bcl-2, Bax and caspase-3. The level of Caspase-3 and Bax mRNA expression after treated by 17-AAG and EGCG was significantly higher, and the level of bcl-2 mRNA expression was lower than that after treated by 17-AAG or EGCG alone. CONCLUSION Our investigation implied that 17-AAG and EGCG in combination can effectively inhibit the proliferation of human nasopharyngeal carcinoma CNE cells. The involved mechanisms may be associated with the upregulation of Bax and Caspase-3 expression.
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of the HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on cell proliferation and apoptosis of human cancer SGC-7901 cells and explore the mechanisms.</p><p><b>METHODS</b>The inhibitory effect of 17-AAG on the proliferation and morphology of SGC-7901 cells was assessed with MTT assay and DNA-PI staining, respectively. Flow cytometry was employed to analyze the changes in cell cycle and apoptosis of the cells following 17-AAG exposure. The cellular expression of Fas protein was detected by immunohistochemistry.</p><p><b>RESULTS</b>17-AAG significantly suppressed the proliferation of SGC-7901 cells in a time- and dose-dependent manner. After treatment with 17-AAG for 48 h, SGC-7901 cells showed cell cycle arrested at G(2)/M stage, and the cell apoptosis rate increased with the 17-AAG concentration. The expression of Fas protein in the cytoplasm of SGC-7901 cells increased gradually with the increase of 17-AAG concentration.</p><p><b>CONCLUSION</b>17-AAG can induce apoptosis, alters the cell cycle distribution and up-regulates the expression of Fas protein in SGC-7901 cells to suppress the cell proliferation.</p>