FBW7, MCL1 Expression And Function In Lung Adenocarcinoma Of Paclitaxel Drug Resistance

BackgroundLung cancer is one of the serious harm tohumanhealth ofmalignant tumor, which is currently the world with the highest morbidity and mortality of cancer. According to the national Ministry of Healthannounced the "Third National Death survey" report, lung cancer has become the first cause of death instead of liver malignant tumors in China(about 22.7% of all malignant tumor death). At present, the treatment of lung cancer by means of operation, chemotherapy and radiotherapy is still the main. Lung cancer, including non-small cell lung cancer( NSCLC) and small cell lung cancer(SCLC) two categories, in patients with non- small cell lung cancer Which accounted for 80% of lung cancer, 65%-80% of NSCLC patients have been diagnosed with locally advanced or metastatic, missed the opportunity of operation. So radiotherapyand chemotherapy are the main treatment for patients with advanced NSCLC. The paclitaxel not only can be used in conjunction with platinum based chemotherapy as first-line treatment, more worthy of attention is, paclitaxel has been considered the gold standard second-line treatment of non-small cell lung cancer. However the emergence of drugresistance greatly limit its clinical curative effect. therefore, in order to further improve the survival and quality of life, on the one hand, to realize individual treatment and the maximum to avoid drug resistance,we need to improve the sensitivity of taxane drugs and explore the effect of predictive factors; on the other hand, continue to explore the new therapeutic target is also a major target for the treatment of NSCLC. Paclitaxel(PTX) is an alkaline substance extracted from the leaves of Taxus plants, research shows that PTX has the antitumor activity is very good, but the PTX resistance restricts its clinical application. myeloid cell leukemia-1(MCL1) is a new member of the Bcl-2 family, plays an important role in the regulation of apoptosis, F-box and WD repeat domain-containing protein7( FBW7) is a tumor suppressor protein, the gene mutation or reduced expression of can be caused by a variety of tumors. In this paper, the relationship between FBW7 and MCL1 detection in lung cancer cells and the level of m RNA and protein levels of taxane drug sensitivity, the potential value of FBW7 and MCL1 as predictors of taxane drug effect, to provide guidance for clinical individual therapy.PurposeTo observe the effects of PTX on the proliferation and apoptosis of human lung adenocarcinoma A549 cells and A549/T cells, assess the expression level of MCL1 and FBW7 protein and m RNA, to explore the potential role of PTX inhibition of lung cancer growth and its drug resistance mechanism.Methods1. The A549 and A549/T cells were treated with PTX at different concentrations in different times. The inhibitory rates of cell proliferation was assessed by MTT.2. After treatment with different concentrations PTX, the m RNAexpression of MCL1 and FBW7 in A549 and A549/T cells was examined by Quantitative real-time PCR(q PCR).3. The protein expression levels of MCL1 and FBW7 in A549 and A549/T cells were examined by Cell immune technique.4. After treatment with different concentrations PTX, the proteinexpression of MCL1 and FBW7 in A549 and A549/T cells was examined by western blotting.Results1. The proliferation of A549 and A549/T cells was inhibited via treatment with different concentrations of PTX in a dose-and time-dependent manner(P<0.05).But the drug concentration of A549/T cells was significantly higher than that in A549 cells.2. After treatment with different concentrations PTX, q PCR showed that the m RNA expression of MCL1 in A549 cells was reduced, whilethe m RNA expression of FBW7 was up-regulated,but there was no obvious change in drug resistance cell.3.Using cell immunohistochemical technique, the expression of MCL1 protein in A549 cells were detected in the lower and A549/T cells, while the expression of FBW7 protein in A549 cells was higher than that of A549/T.4. After treatment with different concentrations PTX, western blotting showed that the protein expression of MCL1 in A549 cells was reduced, while the protein expression of FBW7 was up-regulated,but there was no obvious change in drug resistance cell.Conclusions1.PTXcan inhibit the proliferation of human NSCLC A549 cells and A549/T cells, but the paclitaxel concentration required for A549/T cells was significantly higher than that in A549 cells.2. After treatment with different concentrations PTX, the expression of FBW7 in A549 cells was up-regulated, while MCL1 expression was down-regulated, but the same concentration effect on expression of FBW7 and MCL1 in A49/T cells had no obvious change.3. In A549/T cells, decrease the expression of FBW7 and high expression of Mcl-1 may be associated with paclitaxelresistance,and their possible mechanisms needed further study.