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The AKT/mTOR signaling pathway is a prominent cell-growth promoting pathway that is deregulated in most cancers. Pharmacological inhibition of AKT/mTOR signaling results in cell cycle arrest at the G1 phase and induction of cell apoptosis. 5(6)-Carboxy-X-rhodamine Cyclin D1, c-Myc, and Bmi1 are the downstream targets of AKT/mTOR signaling. Our observation that treatment with TSA and SAHA leads to cell cycle arrest at the G1 phase as well as induction of apoptosis, accompanied by a decrease in the levels of cyclin D1, c-Myc, and Bmi1, suggests that inhibition of HDACs by TSA and SAHA may suppress the activity of the AKT/mTOR signaling pathway. Indeed, after 24 h of treatment, 0.8 ��MTSA and 10 ��MSAHA dramatically diminished the levels of phosphorylated AKT protein without modulation of the total amount of AKT. Similarly, treatment of SGC-996 cells with 0.8 ��MTSA or 10 ��MSAHA for 24 h effectively down-regulated levels of the phosphorylated form of mTOR. In addition, the INK-1117 customer reviews phosphorylation of p70S6K, S6 and 4E-BP1, all of which are markers of the activity of mTOR signaling, was clearly and dose-dependently suppressed by both TSA and SAHA, accompanied with upregulation of the acetylation of histone 3. mTOR kinase is the central integrator and regulator of multiple intracellular signal pathways. Numerous inhibitors of mTOR signaling pathways are undergoing preclinical and clinical trials for the treatment of a wide range of cancers. Among these inhibitors, rapamycin is a wellknown agent. To test whether rapamycin��s inhibition of mTOR signaling leads to a decrease in cell growth and in the proliferation of gallbladder carcinoma cells, SGC-996 cells were treated with different concentrations of rapamycin for 24, 48, and 72 h, with cell viability subsequently determined by MTT assay. Our results showed that rapamycin significantly reduced SGC- 996 cell viability in a dose- and time-dependent manner. The IC50 of rapamycin in SGC-996 cells was 854.1 ��Mfor 24 h, 381.4 ��Mfor 48 h, and 156.4 ��Mfor 72 h. Thus, rapamycin is a promising agent in the treatment of gallbladder carcinoma. In order to assess whether the observed apoptotic effect of HDACIs is related to mTOR path