The effect of DHEA on AKT signal pathway on transplanted Morris hepatomas in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of dehydroepaimdrosterone (DHEA) on the growth of transplanted Morris hepatomas (7288CTC) in vivo in rats.</p><p><b>METHODS</b>21 Buffalo rats were randomly devided into 4 groups, including one blank control group (n = 5), one group for tumor-bearing control (n = 6), and 2 experimental groups with DHEA (n = 6) or DHEA-s (n = 4). DHEA or DHEA-s was fed to the rats for 4 weeks immediately after Morris hepatomas (7288CTC) was implanted in both flanks. Phenotypes of the spleen lymphocytes were examined by flow cytometry, Akt and PTEN expression in tumor cells was detected by Western blot and immunohistochemistry.</p><p><b>RESULTS</b>Tumor weights of DHEA treated group were less than those of the control (P less than 0.05), the inhibitory rate was 43%. The results of Western blot and immunohistochemistry showed that in DHEA tumor group,the expression of phosphorilated Akt protein was decreased, the expression of PTEN was enhanced, the percentage of CD3 positive cells and the ratio of CD4/CD8 were increased (P less than 0.05).</p><p><b>CONCLUSION</b>DHEA can inhibit tumor growth, possibly via the inhibition of the Akt signaling pathway as well as modulating the immune function.</p>

Molecular mechanisms of DHEA and DHEAs on apoptosis and cell cycle arrest via Akt pathway in hepatoma cell lines / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the anti-proliferation effects of dehydroepiandrosterone (DHEAéand DHEA sulfate (DHEAs) on tumor cells.</p><p><b>METHODS</b>Human hepatoblastoma cells (HepG2) and colon adenocarcinoma cells (HT-29) were treated with DHEA and DHEAs of various concentrations. The cells were incubated for 8, 24, 48, and 72 hours, and the proliferation, apoptosis, cell cycle and the expression of phosphorylated Akt (Thr308 and Ser473) were analyzed using MTT assay, flow cytometry, and Western blotting at different time points. The influences of an inhibitor (LY294002) and an activator (hepatic growth factor; HGF) of PI3K on the effectiveness of DHEA were determined in HepG2 cells.</p><p><b>RESULTS</b>By increasing the concentrations of DHEA (1, 10, 50, 100, 200 micromol/L), the percentages of HepG2 and HT-29 survival cells treated with DHEA at 24 h were 92.7%+/-0.9%, 84.7%+/-1.2%, 62.4%+/-0.8%, 49.5%+/-0.8%, 50.7%+/-0.3% and 92.5%+/-0.4%, 89.5%+/-0.7%, 80.5%+/-1.1%, 67.5%+/-1.5%, 70.6%+/-0.6%, respectively. Proliferations of HepG2 and HT-29 cells were significantly inhibited after 24 hours of being incubated with 100 micromol/L DHEA treatment; the inhibition effect was stronger on HepG2 cells than on HT-29 cells. The effect of DHEAs on both cell lines on cell proliferation was weaker than that of the DHEA. In the cell cycle assay, DHEA treatment induced cell arrest in G0/G1 phase in both cell lines. Apoptosis of HepG2 cells was significantly triggered (18.6%+/-2.2%) by 100 micromol/L DHEA treatment for 24 hours, but not by DHEAs. In addition, 100 and 200 micromol/L DHEA treatments for 24 hours markedly inhibited phosphorylations of Akt (Thr308 and Ser473) in HepG2 cells, and these effects were enhanced by exposing them to LY294002 and stopped by exposing them to HGF. The anti-proliferative effects of DHEA on tumor cell lines were much stronger than those of DHEAs, and they were even stronger in HepG2 cells than in HT-29 cells.</p><p><b>CONCLUSION</b>Our results suggest that the induction of apoptosis through the inhibition of Akt signaling pathway is one of the anti-proliferative mechanisms of DHEA in certain tumors, but DHEA also promotes cell-cycle arrest.</p>