| Background and ObjectivesLung cancer is one of the most common malignancies in the clinical, and is currently the biggest threat to human health and life which causes great pain to the patients and family.80%of patients who had been diagnosed as lung cancer were already in late-stage, Even if they were in the early stage of non-small cell lung cancer, only one third of them could be fully cured via surgery. The survival time of most patients who are impossible to be cured differs from a few months to several years, which mainly depends on lung cancer diffusion range, the patient’s general condition, the patient’s response to therapy and the effectiveness of the treatment. So optimization of therapy to improve lung cancer therapy efficiency is the key factor, the molecular targeted therapy is an important treatment method, and several kinds of selective TKIs which has been found recently had a huge impact in tumor treatment, and had curative effect in lung cancer treatment, However, the acquired drug resistance limits the application of these drugs. A lot of molecular mechanisms may be the potential factors that cause drug resistance. In research of lung cancer therapy strategy that won’t cause acquired drug-resistance, understanding the signaling pathway about tumor formation and development and developing inhibitors that aim at the transduction pathway will be hot spot in cancer research and promote the development of clinical cancer treatment. The new drug NVP-BEZ235is PI3K and mTOR double kinase inhibitor, which can competitively bind with ATP enzyme’ combined tank, it had showed good inhibition to a variety of solid tumor, for example breast cancer, renal cancer and so on. Now it has been used in phase1/phase II clinical trials. A number of research have showed that BEZ235could induce tumor degradation, block some disease, enhance other drugs’efficacy when combined with other anticancer drugs, and make radiotherapy more sensitive. In this study we use BEZ235to treat lung cancer cell A549to detect the antitumor activity of BEZ235in vitro and the mRNA expression of akt, mek, erk which will research the role of BEZ235in lung cancer and provide the basis for clinical treatment.Methods1. Lung adenocarinoma cell A549was supplied by the central experiment of the Second affiliated hospita. Cultivate the cells with the RPMI-1640complete culture media containing10%fetal bovine serum in the37℃,5%CO2saturated humidity incubator.2. BEZ235was chosen as the trial drugs.3.Observed the growth of lung cancer cell line A549via the inverted microscope when treated by different time and different drug concentrations.4. MTT assay was used to examine suppressive rate of the growth on A549cell.5. the expression of akt, mek, erk mRNA level were detected by RT-PCR.6.The experimental data were analyzed with SPSS17.0software, experiment will be repeated three times, inspection level α=0.05; P<0.05showed statistically significant difference.Results1. As the time and concentration increased, the inhibition of BEZ235on A549cell strengthened gradually.2. RT-PCR results showed the expression of akt, mek, erk mRNA can be detected in all groups, akt mRNA expression level decreased compared with control group, the difference has statistical significance (P<0.05), and as the time and concentration increased the expression of akt mRNA level gradually decreased; There was no statistically significant difference when comparing the change of mek, erk mRNA expression level with the control group (P>0.05).ConclusionBEZ235can inhibit the proliferation of A549cells and in a concentration and time dependence manner, this inhibition may be related to downgrade of akt mRNA expression level, and has no obvious correlation with the change of mek, erk mRNA level. |
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