Interference Of Lovastatin In Proliferation Of Chronic Myeloid Leukemia Cell

Objective:Chronic myeloid leukemia (CML) is one of malignant clone diseases induced by multipotent hemopoietic stem cell anomalous proliferation. Traditional treatments for CML contain chemotherapy, IFN-αtherapy,transplantation of hematopoietic stem cell and so on. Of which, transplantation of hematopoietic stem cell can cure CML, whereas most people would hard to accept because of its high price and high risk. IFN-αtherapy and chemotherapy just relieve symptoms and will eventually progress to the accelerated phase and blast crisis period. With a definite molecular biology mechanism of CML, mesylate (Imatinib, IM) can treat CML, but its high cost, limited its clinical application. Recently IM-resistant became a new problem. So, how to surmount drug fast and find new effective drug is the hot issue on academics in civil and abroad. Recent studies have found that the traditional the hypolipidemic statin drugs can inhibit the growth of solid tumors. Thus, we choose various IM-resistant and non-IM-resistant CML cell lines, in order to observe the influence of lovastatin in these cell lines and combined with IM to observe whether exist the synergism.Method:(1) Detected the influence of LOV and IM on chronic myeloid leukemia cell growth K562,K562R,32Dp210,32Dp210^Q252H,32Dp210^Y253H,32Dp210^E255K,32Dp210^T315I,32Dp210^M351T cells by MTT. (2) Detected the depressant effect in the growth on K562,K562R,32Dp210,32Dp210^Q252H,32Dp210^Y253H,32Dp210^E255K,32Dp210^T315I,32Dp210^M351T cells stimulated by LOV combination with IM and evaluated synergistic effect.(3)Detected the Apoptosis effect of lovastatin on K562,K562R cells by FCM.Result:(1) LOV on K562, K562R cell inhibition with time and dose increased significantly enhanced(2) LOV on K562, K562R the role of cell apoptosis induced by the increased significantly with the dose increase.(3) LOV on 32 Dp210, 32Dp210Q252H, 32Dp210Y253H, 32Dp210E255K, 32Dp210T315I, 32Dp210M351T inhibit cell proliferation increased significantly with the dose increase.(4) IM on K562, K562R, 32Dp210, 32Dp210Q252H, 32Dp210E255K, 32Dp210M351T inhibit cell proliferation increased significantly with the dose increase.(5) Combined application of LOV and IM on cell inhibition markedly improved, and higher than the separate application LOV or IM in K562, K562R, 32Dp210, 32Dp210Q252H, 32Dp210M351T five cells, and have a synergistic effect (CI <1).Conclusion:(1) Lovastatin can inhibit chronic myeloid leukemia cells in vitro. (2) Lovastatin inhibit the proliferation of the IM-resistant chronic myeloid leukemia cell(3) Combined application LOV and IM have synergies effect in certain mice and human chronic myelocytic leukemia cells.(4) Lovastatin promote the apoptosis of chronic myeloid leukemia cell .