BACKGROUND: One of mechanisms involved in treating cerebral ischemia with bone marrow mesenchymal stem cells (BMMSCs) implantation is paracrine action. However, few studies have reported this mechanism.OBJECTIVE: To observe the inhibitory effect of BMMSCs paracrine action on apoptosis and its mechanism after cerebral ischemia. METHODS: BMMSCs were isolated from rats with adherent culture. Rat cerebral ischemia model was established by the middle cerebral artery occlusion. A total of 24 rats were divided into 4 groups, with 6 animals in each group. Cell implantation medication group: rats were received U0126 medication after BMMSCs implantation; Non-implantation medication group: rats were received U0126 medication after PBS injection; Cell implantation control group: received solvent medication after BMMSCs implantation; Non-implantation control group: received solvent medication after PBS injection. At 7 days after operation, the expressions of vascular endothelial cell growth factor (VEGF) and p-ERK1/2 protein were measured by Western blot analysis, and the apoptosis cells in the area of ischemic penumbra and cortex were examined by TUNEL. RESULTS AND CONCLUSION: The VEGF protein content in the brain tissue was significantly greater in the cell implantation groups than that of the non-implantation group, with increased p-ERK1/2 and decreased apoptosis cells. The expression of p-ERK1/2 was down-regulated in rats which were administrated U0126 while the number of the apoptosis cells was increased, but the VEGF protein expression had no statistical difference. It suggested that BMMSCs can paracrine VEGF in the striatum of brain and play an inhibitory effect on apoptosis in the ischemia area via activating ERK1/2.

OBJECTIVETo investigate the antineoplastic effects of 2-Deoxy-D-glucose (2-DG) combined with Taxol on orthotopically transplanted breast cancer in C3H mice and explore the mechanism.

METHODSC3H mice bearing orthotopically transplanted breast cancer xenograft were randomly divided into 4 groups, namely the control group, 2-DG group, Taxol group, and 2-DG+Taxol group. The corresponding drugs were administered intraperitoneally every 3 days for 18 consecutive days, and the tumor volume was measured every 3 days to draw the tumor growth curve. The mice were then sacrificed to measure the tumor weight on day 19 and examine tumor cell apoptosis with TUNEL assay and VEGF expression using immunohistochemistry.

RESULTS2-DG combined with Taxol obviously suppressed the tumor growth with a tumor inhibition rate of 66.06% as compared to the rate of 36.97% in Taxol group. The combined treatment also caused more obvious cell apoptosis and significantly reduced VEGF expression in the tumor cells as compared with the other groups.

CONCLUSION2-DG can enhance the inhibitory effect of Taxol on orthotopically transplanted breast cancer xenograft in C3H mice probably by inducing tumor cell apoptosis and lowering VEGF expressions.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; Breast Neoplasms ; drug therapy ; pathology ; Cell Line, Tumor ; Deoxyglucose ; pharmacology ; therapeutic use ; Drug Synergism ; Female ; Mice ; Mice, Inbred C3H ; Paclitaxel ; pharmacology ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays