| Malignant glioma is the most common primary malignant tumor in adult; it forms about 33.3-58.9% of intracranial tumors, with an average of 43.5%, characterized by the highest risk of recurrence.With anomalies biological characteristics like invasive, blood vessel-rich, unlimited proliferation and lack of apoptosis, malignant glioma is considered to be one of the most difficult refractory tumors. So far, there is no effective therapy, it makes important theoretical and clinical significance of evaluation the new and efficacious therapeutic methods on malignant gliomas.The purpose of this study was to observe that the effects of DDP combined with Endostatin on ability of proliferation, adhesion and invasion of human glioma cells (U251) cultured in vitro, and provide experimental basis for targeted treatment with conventional chemotherapy combined with anti- angiogenic therapy on malignant glioma. In this study, human glioma cell strain (U251) cultured in vitro was used as experimental model, The experimental methods such as MTT colorimetric assay, Flat cloning, Transwell invasion assay were used to observe the capacity of proliferation, colony formation, adhesion ability and In vitro invasion capacity of U251 cells treated with DDP or Endostar alone and combination of these two Results showed that when DDP alone was used, the inhibition role on U251 cells in vitro was gradually deepening (P<0.01) with increasing of concentration (from 0.625 to 5.0μg/ml )and lengthen of time( from 24 hours to 72 hours). The effect of Endostar on U251 cells in vitro was not very obvious, although when the concentration was 800μg/ml the inhibition effect had statistically significant (P<0.01), but inhibition rate was only for 19.7%. The synergistic inhibition effect of DDP combined with Endostar showed very obvious (P<0.01). The results of Colony-forming assay were fully consistent with results of MTT colorimetric, especially in the low-dose of DDP combined with Endostar .Adhesion of cells is the initiating invasion steps of cancer cells, usually the heterogeneity adhesion capacity between tumor cells which have high invasiveness with basement membrane components is increased, while the ability of homogeneity adhesion of tumor cells is dropped. This feature is the benefit of separating tumor cells from maternal tumor body, and invades normal tissues such as basement membrane. As it showed in this experiment, adhesion rate of control group was 85.6%, of DDP alone was 47.4%, Endostar alone with increasing concentration (from 100 to 800μg/ml), the adhesion rate decreased from 83.2% to 24.6%. When DDP combined with Endostar was used, the adhesion rate continued to decline, reached to the minimum of 8.9%. It meant that, individual effects of Endostar would reduce adhesion of tumor cell obviously, synergistic effect was showed while these two-drug combined (P <0.01).In this experiment, Matrigel was putted on the porous membrane of Transwell invasion chamber, which was similar to the natural basement membrane. The purpose was to observe the ability of U251 cells passing through porous membrane induced by chemotactic agents.The results showed that the number of migratory cells in control group was 358, the group of DDP alone was 157, In the groups of Endostar alone, the number of migratory cells decreased from 201 to 72 with increasing concentration from 100 to 800μg/ml.. When these two-drug combined, number of migratory cells continue to decline, reach to the lowest of 45. It meant that, DDP alone would reduce migration of tumor cell obviously, while these two-drug combined showed s synergistic (P<0.01).As we all know that makes it is difficult for drug to come into tumor owing to blood-brain barrier in malignant brain tumor ,so the effectiveness of chemotherapy of malignant glioma is usually not so well.Anti-angiogenic therapy is a promising anti-tumor treatment strategy, but the anti-angiogenesis agents work against the angiogenesis component directly, so these agents can only stabilize tumor process, but no complete regression. Results of in vivo experiment have proved that targeting tumor cells and endothelial cells by combination of traditional chemotherapy and anti- angiogenesis agents can enhance anti-tumor efficacy. It is more effective than individual effects of each. In this study, the results of in vitro experiment further proved rthat synergistic effect was showed while using DDP combined with Endostar... |
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