Dexamethasone Induced Resistance To Paclitaxe In Adenocarcinoma Of Lung And Expression Of BCL-XL And Survivin Gene

Objective: Chemotherapy is one of the chief means of treating malignantsolid tumors. Glucocorticoid was generally used in lymphatic systemtumors(because it induce lymphocyte to apoptosis),and in some combinedtreatment of tumors(such as, anti-vomit, relieving acute toxicity, preservatingnormal tissues, improving appetite, weight gain, relieving fatigue, relievingosteodynia, relieving urinary tract obstruction, reducing generation of adrenalandrogen and anti-edema during chemoradiation). But, new data indicated thatglucocorticoid induce majority of malignant solid tumors to chemo-resistanceand radio-resistance. But,there were some of problems which need to be resolve,for example, chomo-resistance if related to concentration of glucocorticoid, andif related to gene expression of anti-apoptosis, such as, Bcl-xL、Survivin. Tosolve these problems, can help to provide theory accordance for choosingchemotherapy regimens, in clinical, and using correctly ancillary drugs,avoiding abuse of glucocorticoid, and reducing chemo-resistance, andlengthening patients’ survival, and for searching target point of gene regulationthat can inverse chemo-resistance which induced by glucocorticoid.Methods: The cells viability rate of lung adenocarcinoma A549cells wasdetermined by MTT assay (mononuclear cell direct cytoxicity assay) after treatment of different concentrations of paclitaxe(PTX), and to estimate theconcentration of IC50of PTX. The cells viability rate of A549cells whichpretreated with different concentrations(respectively0.1,1,10μ mol/L) ofdexamethasone(DEX) was determined by MTT assay after treatment of differentconcentrations(respectively1×IC50and2×IC50，IC50:28.66μmol/L) of PTX,and the expression level of mRNA and protein of Bcl-xL and survivin in all ofthe A549cells were determined by reverse transcriptase-polymerase chainreaction(RT-PCR) and Western Blot. Statistical analysis: Analysis of data wasperformed using the computer software Statistical Package for Social Sciences(SPSS) for Windows (version17.0). The experimental data was measurementdata, to express as x±s, and the Comparison among over2groups by analysisof variance(ANOVA), and between two groups by LSD-t test. A two–tailedp<0.05was considered statistically significant.Results: After being pretreated with DEX in different concentrations，A549cells were induced resistance to PTX，and survival rate of A549cellswasincreased, and the rate of drug-resistance increased gradually with the increasingconcentrations of DEX and the expression level of Bcl-xL and survivin mRNAand protein increased gradually with the increasing concentrations of DEX also.Conclusions: Dexamethasone can induce resistance to paclitaxel in lungadenocarcinoma cells，and the mechanism may be that Dexamethasone inducedBcl-xL and survivin mRNA and protein express up-regulation, and the cellularapoptosis was reduced.