| Nowadays, lung cancer is the highest incidence of malignant tumor. In male patients, it's the highest mortality and in female patients, it's has been the number one killer more than breast cancer in some developed country. Non-small cell lung cancer (NSCLC) is most common histopathologic type in lung cancer, about 85%. As for stage Ia-IIIa, surgery is the most common treatment. After surgery, platinum-based combination chemotherapy and radiotherapy when necessary is the standard adjuvant therapy. As for stage ?b-?, relapse and transfer patients, chemotherapy, target therapy and immunotherapy are main treatments.However, overall survival of lung cancer is still low, even worse than most malignant tumor. The poor efficient, high adverse reaction rate, pool tolerance and drug resistance of medicine are main problems which are urgent to be solve. Therefore, developing new antitumor drug target and provide a new way of research are key work of scientific researchers.Piceatannol and its analogues are a kind of stilbene derivative, which can be extracted from grape, rheum, sugarcane and so on. Piceatannol and its analogues, contains resveratrol, pinosylvin, et al, have the same pharmacological and functional characteristics. These medicines have the function of antioxygenation, removing oxygen free radicals, and protecting the cardiovascular system. In addition, some researchers found that piceatannol also have the activities of antitumor recent years. Therefore, deeper research of piceatannol and its analogues will provide new thoughts and approaches for the therapeutic of malignant tumors. Here, we review the progression of structural and functional characteristics and antitumor activities of piceatannol and its analoguesGemcitabine is a kind of cytarabine, Cell-cycle kinetic studies have shown that gemcitabine is most active during the S phase. Apart from inhibiting DNA synthesis, the self-potentiation is also its character. It is validated that the response rate of the single-agent gemcitabine was consistently above 20%, median survival was 34 weeks and could improve the disease-related symptoms with well-toleranced toxicities and is an effective and relatively economic selection for the treatment of advanced NSCLC. This report reviews the clinical studies of gemcitabine in the patients with advanced NSCLC.Programmed cell death is regulated by various apoptosis related molecules death procedure which is closely related with development, self stability, the occurrence and development of malignant tumors, autoimmune diseases and other diseases. Bcl-2 protein family is the main control factor to control mitochondria to release the apoptotic factors. In the absence of a death signal stimulation, Bcl-2 and Bcl-xl anti apoptotic protein were isolated as an integral membrane protein membrane organelles, and Bak, Bad and other pro apoptotic protein located in the cytoplasm or mitochondrial membrane in the form of non active. When cells were stimulated by a death signal, pro apoptotic protein change the spatial conformation and interact between anti apoptotic protein in membrane, so the anti apoptotic protein lose the inhibition of apoptosis, thereby induce programmed cell death.The Cancer Genome Atlas (TCGA) includes different types of genome data information in 33 types of cancer which come from 11000 patients, such as mutation, gene expression, DNA methylation, mutation copies. Therefore, we can research cancer genomics from different levels. The normal download pathway is Data Portal including 4 levels data:1 level (original data); 2 level (processed data); 3 level (segmented/interpreted data); 4 level (summary/regions of interest). In this article, we downloaded lung adenocarcinoma data, then grouped cases and analyzed survivals.Part 1 The relationship between Bcl-2, Bak, Bad, Bcl-xl mRNA' levels and lung adenocarcinoma patients'survivalPurpose:In order to speculate the relationship between the expression of Bcl-2, Bak, Bad, Bcl-xl mRNA and lung adenocarcinoma patients' survival.Method:We downloaded more than 200 lung adenocarcinoma (stage ?-?) cases including general data, follow-up time, gene expression and other data in TCGA database. After selecting, total 279 cases was included. We chose Bcl-2, Bak, Bad, Bcl-xl mRNA to analyse the relationship between the expression and lung adenocarcinoma patients' survival by making Kaplan-Meier survival curve and using log-rank test to compare survival rates. We use ?=0.05 as significant level, p< 0.05 asstatistical significance.Result:1. As for stage Ia-IIIa cases, patients' mOS was 1026.0 days with high Bcl-2 expression and 922.0 days with low Bcl-2 expression. High expression of Bcl-2 mRNA was significantly corresponding with long mOS, p=0.016. Patients' mOS was 949.0 days with high Bad expression and 995.0 days with low Bad expression. The expression of Bad mRNA was not significantly corresponding with patients' mOS, p=0.805. Patients'mOS was 950.0 days with high Bak expression and 952.0 days with low Bak expression. The expression of Bak mRNA was not significantly corresponding with patients'mOS, p=0.752. Patients'mOS was 950.0 days with high BCLXL expression and 987.0 days with low BCLXL expression. The expression of BCLXL mRNA was not significantly corresponding with patients' mOS, p=0.606.2. As for stage ?b-? cases, patients' mOS was 697.0 days with high Bcl-2 expression and 976.0 days with low Bcl-2 expression. Patients with low Bcl-2 expression live longer than high expression, while there was no significantly difference, p=0.06. Patients' mOS was 1043.0 days with high Bad expression and 826.0 days with low Bad expression. The expression of Bad mRNA was not significantly corresponding with patients' mOS, p=0.641. Patients' mOS was 1043.0 days with high Bak expression and 826.0 days with low Bak expression. The low expression of Bak mRNA was significantly corresponding with patients' long mOS, p=0.290. Patients' mOS was 1043.0 days with high BCLXL expression and 826.0 days with low BCLXL expression. The expression of BCLXL mRNA was not significantly corresponding with patients' mOS, p=0.785.Conclusion:For these cases(Ia-IIIa lung adenocarcinoma) discussed in this study, the mRNA level of Bad and Bak, has no statistical significances with patients' prognosis; while the mRNA level of Bcl-xl can be seen as an important factor which is able to be used to predict patients' prognosis. For these cases(IIIb-IV lung adenocarcinoma) discussed in this study, the mRNA level of Bcl-2, Bad and Bak, can be seen as important factors which are able to be used to predict patients' prognosis.Part 2 Piceatannol Enhances the Antitumor Efficacy of Gemcitabine in HumanA549 Non-Small Cell Lung Cancer CellsObjective To enhance the anticancer efficacy of gemcitabine in the treatment of non-small cell lung cancer (NSCLC), search appropriate targets for new medicine and enhance efficacy in the treatment of lung cancer, the potential synergistic effect of piceatannol on gemcitabine cytotoxicity was investigated in the human NSCLC A459 cell line.Methods The A549 cells was divided into 4 groups:control group; dealing with piceatannol; dealing with gemcitabine; dealing with piceatannol and gemcitabine. The MTT cell viability assay showed that piceatannol significantly enhanced the cytotoxic effects of gemcitabine by lowering the gemcitabine IC50 value. Flow cytometry analysis revealed that piceatannol exerted its pharmacological effect mainly by increasing the late apoptotic population. Western blot analysis showed that gemcitabine induced the expression of the proapoptotic proteins Bad and Bak, and pretreatment with piceatannol further increased Bak expression, leading to an increased number of cells undergoing late apoptosis.Results The MTT cell viability assay showed that piceatannol significantly enhanced the cytotoxic effects of gemcitabine by lowering the gemcitabine IC50 value. Flow cytometry analysis revealed that piceatannol exerted its pharmacological effect mainly by increasing the late apoptotic population. Western blot analysis showed that gemcitabine induced the expression of the proapoptotic proteins Bad and Bak, and pretreatment with piceatannol further increased Bak expression, leading to an increased number of cells undergoing late apoptosis.Conclusions The findings from this study show that piceatannol can enhance the cytotoxic effects of gemcitabine by enhancing expression of the proapoptotic protein Bak, thereby providing the rational basis for a novel combination strategy for the treatment of NSCLC. |
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