Nuclear Factor-κB Decoy Oligodeoxy Nucleotide Combined With Paclitaxel In The Treatment Of Lung Cancer

Background:Lung cancer is a serious threat to harm human health and life of the malignant tumor, according to the results of epidemiological studies in recent years, incidence and mortality lung cancer is rising, according to statistics, the incidence of all malignant tumors accounted for 12%. Some countries in Europe, America and our cities, the incidence rate has primacy, and the younger age of onset tends to, and smoking, environmental pollutants are closely related, the treatment is difficult, rapid transfer, high mortality characterized. Tumor invasion and metastasis has become the lead to treatment failure and the leading cause of death in patients, so look for the key target sites of angiogenesis inhibition of lung cancer, for lung cancer treatment to open up a new way.Nuclear factor (nuclear factor- kappa B, NF-kB) is a multi-dominant gene transcription factor, and transcription of multiple genes closely related to high expression in tumor cells, with a variety of cellular gene promoter and enhancer specific binding occurs, and cyclooxygenase 2 (Cyclooxygenase -2,COX2), vascular endothelial growth factor (Vascular endothelial growth factor,VEGF) is closely related, is involved in inflammation, injury stress, immune defense, cell proliferation and apoptosis process. NF-kB decoy oligodeoxynucleotide (NF-kB decoy ODN) is carried out in vivo study found a powerful tool for gene regulation, transcription factor recognition sequence containing oligonucleotides or plasmids into cells, and nuclear genes the role of the promoter region of the corresponding advantage of the opportunity component competitive binding transcription factor, thereby inhibiting the activation of the promoter, to inhibit gene transcription and translation purposes, its value can inhibit cancer cells, and enhance the tumor cells to chemotherapeutic drugs (paclitaxel) sensitivityObjective:Research NF-kB decoy oligodeoxynucleotide (NF-kB decoy ODN) combined with paclitaxel on lung cancer A549 cell proliferation, apoptosis, angiogenesis and its mechanism of action, provide the theoretical basis for clinical practice.Methods:1. Cultivate human lung cancer cell A549.2. Using liposome-mediated transient transfection method full phosphorothioate NF-kB decoy oligonucleotides (decoy ODN), and all missense phosphorothioate decoy oligonucleotides (scramble decoy ODN) treatment A549 cells.3. MTT test interventions observed 96 h after NF-kB decoy ODN and NF-kB Scramble decoy ODN role in lung cancer A549 cells after growth curve.4. Divided into the control group, NF-kB decoy ODN group, paclitaxel group (1000ng/ml) and NF-KBdecoy ODN + paclitaxel group, RT-PCR method to measure the level of Cyclooxygenase -2(COX-2)mRNA expression measured by immunohistochemistry the expression of Vascular endothelial growth factor (VEGF) protein in the flow Type cells 48 h after surgery to detect the apoptotic rate. Results:1. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) significantly inhibited the cell growth, the more obvious the longer inhibited.2. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN), paclitaxel A549 cells after the intervention levels of Cyclooxygenase -2(COX-2)mRNA expression and VEGF protein expression decreased, COX-2 mRNA expression levels of concentration in each group were:0.71±1.4μg/μL,0.44±1.8μg/μL,0.51±7.2μg/μL,0.34±9.5μg/μL (F=7.8, P<0.05), Vascular endothelial growth factor(VEGF) protein expression positive rate of cells in each group were:85±0.50%,63±0.26%,57±1.5%,21±0.34%(F= 21, P＜0.05).3. NF-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) combined with paclitaxel can promote apoptosis of A549 cells, the two together were synergistic or additive effect with each group the apoptosis of cells is:(16.8±0.01)%, (5.6±0.02)%, (32.6±0.04)%, were higher (6.0±0.02)%(F=14, P<0.05).Conclusion:1. Nuclear factor-κB decoy oligodeoxynucleotide (NF-κB decoy ODN) significantly inhibited the growth of lung cancer A549 cells.2. The nuclear factor-κB snare widowed deaeration nucleotide (NF-κB decoy ODN) unites the taxus mellowly to be possible to suppress the lung cancer A549 cell's growth obviously, this function is possible and epoxy synthase-2 (COX-2), blood vessel bast growth factor (VEGF) expression related.3. The nuclear factor -κB snare widowed deaeration nucleotide (NF-κB decoy ODN) unites the taxus mellowly to be possible to strengthen the induction which and perishes weakly to lung cancer A549 cell multiplication's suppression, the two have coordinate the anti-tumor function...