The Treatment Of Super Interferon Alpha On Non-small Cell Lung Cancer

Despite significant improvements in prevention, lung cancer remains the most common cancer in China as well as the leading cause of cancer-associated death worldwide. There are many types of lung cancer and each type of lung cancer grows and spreads in different ways and is treated differently, according to its pathological features, lung cancer can be divided into small-cell lung carcinoma (SCLC, approximately 25%) and non-small-cell lung carcinoma (NSCLC,75%). Nowadays, the treatments of NSCLC are mainly performing surgical resection assisted by radiotherapy and chemotherapy. However, this therapeutic strategy appears a lot of shortcomings. For example, surgical resection is just directed against early stage of cancer which is difficultly detected by nowdays diagnostics. Furthermore, the following radiotherapy and chemotherapy may bring various side effects, such as nausea, vomiting, hair loss, fatigue and also they are myelosuppressive, nephrotoxic and cardiotoxic.Biotherapy, the fourth oncotherapy following surgical resection, radiotherapy and chemotherapy, is a strategy of cancer treatment by using biological response modifiers (BRM). In general, there are four types of biotherapy including cell therapy, cytotoxic therapy, gene therapy and antibody therapy. And biological agents widely used in clinic contain interferon (IF), interleukin (IL), tumor necrosis factor (TNF) and so on. Among these, interferon is the first cytokine that approved for clinical treatment by FDA. Interferons are proteins made and released by host cells in response to the presence of pathogens, and their activities are regulated by cell genome and also involves in RNA and protein synthesis. Based on gene sequences, chromosomal localization, and the type of receptors, human interferons have been divided into three major types:typeⅠ,ⅡandⅢ. Interferon typeⅠis the most complicated which includes IFN-α,β,ω,ε,κ,δ,τ,ξ. Among typeⅠinterferons IFNa is the most commonly used which can be divided as IFNα-1a,1b 1c,1d, IFNα-2a,2b,2c and so on. The typeⅡis IFN-y, which is also known as immune interferon and the typeⅢis a newly discovered cytokine which is regarded to be closely associated to the typeⅠ. All interferons show a wide variety of biological functions such as antiviral, immunoregulatory as well as antitumor.Super interferon alpha (sIFNα) is a newly recombined artificial interferon. In this study, we focused on investigating the effects of it on a human NSCLC cell line A549. By the strategy of using sIFNa to treat A549 in vitro and in vivo, we got good results:1. MTT assay and crystal violet staining preliminary demonstrated that sIFNa could significantly inhibit the growth of A549 tumor cells and decrease the viability of them.2. To further confirm the growth inhibition effect of sIFNa, the growth states of the cells were detected using the IncuCyte instrument, and cells treated with sIFNa showed enlarged cell size and flatted morphology.3. Hoechst 33258 staining assay, flow cytometry, western blot and TUNEL detection showed that sIFNa can not evoke cell apoptosis in A549 in vitro.4. Senescenceβ-Galactosidase Staining showed that sIFNa may induce cellular senescence in A549 in vitro.5. A model of A549 human lung tumor xenograft was established on athymic nude mice to investigate the antitumor efficacy of sIFNa in vivo. Results showed that the growth of sIFNa-treated tumors was significantly suppressed. And the immunohistochemical staining was carried out for detection of cellular senescence in vivo.6. Through the western blot and immunofluorescence we thought that the mechanism of sIFNa induced senescence may be related to accumulation of p53 and p21.In conclusion, sIFNa could inhibit tumor growth in a moderate way of inducing cellular senescence that not only effectively decreases the side effects and patients' suffering, but also improve patients'life quality and longevity. Therefore, sIFNa is a promising anticancer drug in future life.