Western blot for PTEN, phosphorylated Akt, total Akt, phospho PDK1 and PDK1 as a whole. FTY720 Fingolimod b-actin expression served as a loading control. doi: Synergy 10.1371/journal.pone.0026343.g002 mTOR and PI3-kinase inhibitor fourth October 2011 | Volume 6 | Issue 10 | e26343 we suggested k nnte resistance to the inhibition of mTOR to overcome. The combined treatment inhibits cell growth in synergy in endometrial cancer cell lines and hyper BEZ235 ZSTK474 After the demonstration, low efficiency in the regulatory s temsirolimus-induced Akt phosphorylation, we examined the combined antiproliferative treatment with temsirolimus or BEZ235 ZSTK474. A plurality of cans or ZSTK474 BEZ235 alone or in combination with temsirolimus were tested to determine the optimal concentration to induce growth-inhibitory effects.
Rst Were the group of buildings Rmutterschleimhautkrebszellen with a drug treatment and compared to mine Trise vehicle. BEZ235 alone reduces cell proliferation by 50% at doses as low as 1 to 50 nm ZSTK474 solely cytostatic in all eight cell lines tested endometrial cancer, cell growth is inhibited Deforolimus to about 100 1000 nm. If, however, was combined with low-dose ZSTK474 BEZ235 or temsirolimus, cell proliferation in a synergistic manner with respect to BEZ235 or ZSTK474 was inhibited alone. Remarkably, was a 50% reduction in proliferation with temsirolimus combined BEZ235 and at a lower concentration of BEZ235 in Figure 3 Temsirolimus-induced Akt phosphorylation was reduced by BEZ235 and ZSTK474, but not by AZD6244. A, H and Ishikawa cells were cultured for 24 hours are Hec50co and treated overnight with the indicated inhibitors.
Phospho Akt and total Akt were determined by Western blot. B, were endometrial cancer cell lines with inhibitors indicated for the night treated. Total protein extracts were analyzed by Western blot for P S473 Akt and total Akt or phospho T389 p70S6K and total p70S6K analyzed. Blots for phospho-Akt Hec1A and KLE cells were subjected to long exposure to low levels of Akt phosphorylation view. doi: Synergy 10.1371/journal.pone.0026343.g003 mTOR and PI3-kinase inhibitor, 5 October 2011 | Volume 6 | Issue 10 | e26343 with BEZ235 alone. Handling co ZSTK474 with 1 nM temsirolimus resulted in a dose- Ngigen synergistic effect on cell proliferation in Hnlichen concentrations BEZ235 with temsirolimus.
The synergistic effect was observed in all cell lines au He KLE, in which the drug combinations had observed an additive effect. Combined indices were calculated and are presented in Table S1 support. These data demonstrate that inhibition of the two components is in front of and behind the PI3K/Akt / mTOR signaling an effective approach to reduce cell proliferation in synergy. Co-operation with temsirolimus BEZ235 or ZSTK474 induced G1 cell cycle arrest and p27 regulation and to temsirolimus BEZ235 been reported to inhibit the growth of cancer cells by inducing G0/G1 cell cycle. Since we have two populations of cells, their proliferation will have differently affected by the treatment temsirolimus, w We hlten repr two Sentative cell lines as models to test the combined approach of cell cycle progression. Content analysis of the cell cycle AN3CA shown that treatment percent of the cells temsirolimus Fig obtained Ht