Affect And Mechanisms Of Small Molecule Compounds S1-Induced Apoptosis In K562 Cell

Objectives: S1, a novel small apoptosis inducer, was designed and synthesized by State Key Laboratory of Fine Chemicals, Dalian University of Technology. The laboratory has its way with the interaction of DNA, damage mechanisms and cytotoxicity were studied, has already applied to the national patent. The vitro experiments have confirmed that the small molecule compounds can induce breast cancer cell line MCF-7, cervical carcinoma cell line Hela and the tongue squamous cell carcinoma cell line Tca apoptosis, Also, the vivo experiments have confirmed that the small molecule compounds can lead tumor size in mice to smaller. But not yet used in leukemia cells, Based on the above, our experiments are intended to use S1 in human leukemia cell line, In order to observe the effect, and further study related mechanisms. Broaden the application range of small molecule compounds, for the treatment of leukemia search for new potential drugs.Method: We used K562 cell line. Cell growth condition was observed by inverted phase microscope. Cells were seeded in 96-well plates at a density of 20,000 per well for k562 cell lines. Cells were incubated with various concentrations of S1, Each experimental condition was done in triplicate and repeated at least once. The growth condition of drug groups are worse than the control group; Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)- 2, 5-diphenyl etrazolium bromide (MTT) assay; Cell viability was measured by MTT assay.We used the Chou-Talalay method to determine the compound combination synergism. the Chou-Talalay method uses the following equation: combination index (CI) = (D)1/(Dx)1 + (D)2/(Dx)2, where (D)1 and (D)2 are the doses of drugs 1 and 2 that have x effect when used in combination; and (Dx) 1 and (Dx)2 are the doses of drugs 1 and 2 that have the same x effect when used alone. The combination isadditive when CI equals 1.0, synergistic when CI is <1.0, and antagonistic when CI is >1.0; T he cell cycle were analyzed by FACScan analysis using CellQuest software; The expression of Bcl-2 protein was examined with western-blotting.Results: The growth condition of drug groups are worse than the control group, The Small molecule compounds can inhibit cell growth. we found that the efficacy of S1 and Arc- in inducing myeloma cell apoptosis in a dose dependent manner. Aslo, We next studied the drug combination effect of S1 with Arc- have a synergistic combination effect at these concentrations. Cell cycl analysis indicated the increased Sub-G1, proportion as well as the apparent G2/M phase arrest (P<0.05) in S1 treated cells.S1 coμld down-regμlate the expression of Bcl-2.Conclusions: We observed that the novel small apoptosis inducer could can inhibit cell growth, which were incubated with various concentrations of S1. Aslo, S1 with Arc- have a synergistic combination effect at different concentrations. S1 induces apoptosis in K562 cells by increasing Sub-G1, proportion and down-regμlate the expression of Bcl-2.