The Effect And Mechanism Of YM155 In Chemosensitivity Of Breast Cancer And Lung Cancer

Backgroud:Cancer is a common and the most serious harm to human health of a group of diseases. The most common and serious harm of tumors of the lung, breast, stomach cancer, liver cancer, cervical cancer, leukemia, lung cancer is the most common among the highest mortality of cancer, and breast cancer is the Chinese women suffering from the most common malignant tumors. Our previous study found that apoptosis inhibitory protein(inhibitor of apoptosis protein, IAP) family members--survivin, its protein levels upregulated in doxorubicin-resistant and highly metastatic breast cancer cells, suggesting that survivin in breast cancer survival and transfer plays an important role. After YM155, survivin inhibitor targeting,application YM155, we found that breast cancer cells survivin expression was significantly down-regulated. Therefore, we hypothesized that YM155 possible to promote tumor cell apoptosis through inhibition of survivin, increase the sensitivity of tumor cells to chemotherapeutic drugs plCancer is a common disease, cancer is the most serious harm to human health of a group of diseases. The most common and serious harm of tumors of the lung, breast, stomach cancer, liver cancer, cervical cancer, leukemia, lung cancer is the most common among the highest mortality of cancer, and breast cancer is the Chinese women suffering from the most common malignant tumors. Our previous study found that apoptosis inhibitory protein(inhibitor of apoptosis protein, IAP) family members--survivin, its protein levels upregulated in doxorubicin-resistant and highly metastatic breast cancer cells,suggesting that survivin in breast cancer survival and transfer plays an important role.After YM155, survivin inhibitor targeting, application YM155, we found that breast cancer cells survivin expression was significantly down-regulated. Therefore, we hypothesized that YM155 possible to promote tumor cell apoptosis through inhibition of survivin, increase the sensitivity of tumor cells to chemotherapeutic drugs play an important role in the survival and the treatment of malignant tumor cellsay an important role in the survival and the treatment of malignant tumor cellsPurpose:In vitro cytology assay YM155 pro-apoptotic effects of four different biological characteristics of tumor cell lines(two kinds of lung cancer cells and two kinds of breast cancer cells), as well as detecting whether YM155 enhancement of tumor cells to chemotherapeutic drug Taxol(Paclitaxel, PAC) sensitivity and elaboration of YM155 sensitivity of different possible causes and mechanisms of different tumor cells.Method:1. In vitro experiments such as MTT, colony formation assay to detected effects of YM155 and paclitaxel alone or in combination in four tumor cell proliferation arising;2. In vitro experiments such as MTT, colony formation, apoptosis, cell cycle assay to observe the role of YM155 in different concentrations at the time of its four tumor cell proliferation, apoptosis, cycle generated and observed four tumor cell of the YM155 sensitivity if different;3. In vitro experiments such as western blot, qRT-PCR to detected P53, survivin,NF-κB pathway and other indicators, analyzes the sensitivity difference YM155 proapoptotic mechanisms.Result:1. YM155 with the chemotherapy drug paclitaxel inhibited tumor cell proliferation,while YM155 in combination with paclitaxel exhibited inhibitory effect was significantly better than paclitaxel alone;2. YM155 killing effect on tumor cells in a concentration-dependent manner with increasing concentration of killing effect on tumor cells also increases. And different p53 status of tumor cell also show different sensitivity to YM155. p53 wild-type tumor cell sensitivity YM155 is lower than that of mutant p53 or p53-deficient tumor cells;3. P53 status of different tumor cell-induced MDM2 role YM155 produced on notthe same. At low concentrations of YM155 stimulation, P53 wild type MDM2 in tumor cells increased the level of transcription, YM155 as survivin targeting specific inhibitors can still reduce the expression of survivin.Conclusion:1. YM155 increase the sensitivity of tumor cells to chemotherapy drug paclitaxel2. Cancer cells of different p53 status showed different sensitivity to YM1553. The role of YM155 is difference because the regulation of p53-dependent MDM2...