Combination therapy of FK228 with rapamycin synergistically promotes human breast cancer cell apoptosis by DNA damage and cell cycle arrest / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the depressant effect of FK228 combined with rapamycin on the human breast cancer cell line MCF-7 and MDA-MB-435.METHODS:FK228, a new histone deacetylase inhibitor, and rapamycin, the specific inhibitor of the mammalian target of rapamycin ( mTOR) protein, were used in the study.MCF-7 cells and MDA-MB-435 cells were exposed to different concentrations of FK228 and rapamycin.The inhibitory rate of cell growth was de-termined by SRB assay.Combination index ( CI) was used to evaluate the interaction between FK228 and rapamycin.The expression of the apoptotic proteins, cycle proteins and nucleic acid proteins were detected by Western blotting.The cell cycle was analyzed by flow cytometry.RESULTS: Both FK228 and rapamycin showed growth inhibitory effects on the breast cancer cell lines in a time-and dose-dependent manner.CI of the 2 drugs was less than 1 when the inhibitory rate of the cell growth was 50%effective dose (ED50)~ED70, indicating a synergistic effect.The combination therapy of FK228 with rapamycin increased the apoptotic proteins, and induced the down-regulation of phosphorylated Akt and over-expres-sion of caspase-3 compared with a single use of the drugs.The combination therapy of FK228 with rapamycin reduced the cycle proteins, and the cell cycle was arrested in G2/M.The levels of phosphorylated H2AX and acetylated H3 were ob-viously increased after combination therapy.CONCLUSION:The combination therapy of FK228 with rapamycin inhibits the cell proliferation and increases apoptosis with a synergistic effect, which may become a new trend for treating endometri-al cancer.

Synergistic Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma in Streptozotocin-Induced Diabetic Rats

BACKGROUND: Diabetic wounds are a major clinical challenge, because minor skin wounds can lead to chronic, unhealed ulcers and ultimately result in infection, gangrene, or even amputation. Studies on bone marrow derived mesenchymal stem cells (BMSCs) and a series of growth factors have revealed their many benefits for wound healing and regeneration. Platelet-rich plasma (PRP) may improve the environment for BMSC development and differentiation. However, whether combined use of BMSCs and PRP may be more effective for accelerating diabetic ulcer healing remains unclear. OBJECTIVE: We investigated the efficacy of BMSCs and PRP for the repair of refractory wound healing in a diabetic rat model. METHODS: Forty-eight rats with diabetes mellitus induced by streptozotocin were divided into four groups: treatment with BMSCs plus PRP, BMSCs alone, PRP alone, phosphate buffered saline. The rate of wound closure was quantified. A histopathological study was conducted regarding wound depth and the skin edge at 7, 14, and 28 days after surgery. RESULTS: Wound healing rates were significantly higher in the BMSC plus PRP group than in the other groups. The immunohistochemistry results showed that the expression of platelet/endothelial cell adhesion molecule 1, proliferating cell nuclear antigen, and transforming growth factor-beta1 increased significantly in the BMSC plus PRP group compared to the other treatment groups. On day 7, CD68 expression increased significantly in the wounds of the BMSC plus PRP group, but decreased markedly at day 14 compared to the controls. CONCLUSION: The combination of BMSCs and PRP aids diabetic wound repair and regeneration.

Mechanism of inhibitory effect of P7 on 3T3 cell proliferation induced by basic fibroblast growth factor / 药学学报

To investigate the mechanism of inhibitory effect of a novel bFGF antagonist peptide isolated from the phage display random heptapeptide library on cell proliferation induced by basic fibroblast growth factor. The effect of P7 on cell morphology was observed under an inverted microscope. Flow cytometry was applied to analyze the effect of P7 on cell cycle progress of bFGF-stimulated cells. The effect of P7 on bFGF-induced activation of MEK and Erk1/2 in MAPK pathway was detected by Western blotting. The results showed that no significant cell morphology change was observed in the range of detected concentrations of P7. Cell cycle analysis showed that P7 decreased S-phase cell population and arrested cell cycle at the G0/G1 phase of bFGF-stimulated cells. The results of MAP kinase activation assay indicated that P7 decreased bFGF-induced MEK and Erk1/2 phosphorylation in a dose-dependent manner. P7 inhibited proliferation of bFGF-stimulated Balb/c 3T3 cells possibly via cell cycle arrest at the G0/G1 phase and down-regulation of signal molecular activation in MAPK pathway.