Docetaxel is a semi-synthetic anticancer drug processing from the European yew needles extract. Its structure is similar to paclitaxel. Sources of docetaxel are more accessible compared with paclitaxel.
The killing effect of certain tumor is 2 times than that of paclitaxel. It is still valid to some resistant cells of over-expression of P-glycoprotein. But the role of docetaxel in gastric cancer cells can not be fully understood.
Docetaxel significantly inhibited MKN45 cells with increasing concentrations. The inhibition of MKN45 cells was significantly enhanced. Gastric cancer cells to different concentrations of docetaxel treatment, the cells were collected, respectively, by agarose gel electrophoresis and TUNEL assay results showed that the apoptotic index of treated cells was significantly higher, DNA gel electrophoresis showed obvious ladder map, and concentration-dependent manner.
Docetaxel-treated cells, the cells were collected at different times, respectively, using real-time quantitative PCR and Western blot analysis. The results showed that, compared with the control group, treated mRNA and protein levels were significantly lower. Docetaxel has been used in clinical treatment of gastric cancer, but the mechanism of action of gastric cancer cells is not fully understood. The scientists used to docetaxel treatment MKN45 cells from apoptosis and survival gene.
Apoptosis in the regulation of cell proliferation, plays a key role in tumor formation and development. With different concentrations of docetaxel treatment of gastric cancer cells, cells were collected at different times, respectively, found using TUNEL and agarose gel electrophoresis, treated cells showed significant apoptosis was time-and concentration-dependent manner. At the same time, the malignant proliferation of gastric cancer cells was inhibited, and the concentration of the drug. These results indicate that gastric cancer cell proliferation was inhibited, and may be related to induction of apoptosis.
There are two classic apoptotic pathways, namely the death receptor pathway and mitochondrial pathway. Inhibitor of apoptosis protein family is from the inhibition of apoptosis in apoptosis signal transduction pathways of these two. Survival factors are an important member of the IAP family. The study found that survivin is rarely expressed in the differentiation and maturation of cells and tissues, but highly expressed in embryonic tissue and not fully differentiated tissues, high expression in a variety of tumor tissues, including lung, breast. Survival factors expression and tumor resistance enhancement and patient survival in non-small cell lung cancer, stomach cancer, neuroblastoma, to lower them. High expression of survivin in gastric cancer tissues, while no expression in adjacent tissues. This high expression was positively correlated with apoptotic index decreased, and tumor invasiveness of gastric cancer.
After docetaxel’s treatment on gastric cancer cells, the scientists test the PCR and Western blot analysis of mRNA and protein levels. Pharmaceutical raw materials suppliers find that the in treatment groups, the survival protein and mRNA decrease. In addition to the decreasing of survivin expression, the level of tumor cell apoptosis has a corresponding rise. According to the statistical analysis, they show a positive correlation. Survivin plays an important role in docetaxel-induced apoptosis of gastric cancer. The study declares that in vitro, docetaxel can significantly inhibit the proliferation of gastric cancer cells. Its mechanism may be related to induction of apoptosis and downregulation of survivin gene expression.
Source:http://www.cospcn.com
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