| Background：Lung cancer is now the one of leading cause of cancer death, and dying innon-small-cell lung cancer (NSCLC) accounted for of the most patients. The studyindicated that there were a lot of mast cells and capillaries around the tissue ofNSCLC. The mast cells are the main inflammation-mediated cell of the body, whichcan secrete inflammatory mediators including an array of cytokines, chemokines,proteases, and histamine. Strouth et al.[1] proved that mast cells around cancerorganizations played an important role in the growth and progression of cancer.Vascular epidermal growth factor (VEGF) and IL-8secreted by mast cells promotethe tumor cell growth and division, the angiogenesis around the tumor tissue, whichprovide favorable conditions for the deterioration of the tumor. Therefore reducingthe number of mast cells around cancer organizations or inhibiting the production orrelease of the relating proinflammatory cytokines may be the effective and novelmethod for cancer treatment.Mast cells express high-affinity for IgE receptor (FcεRI). Base on this, atargeted toxins (Ig-Fc-PEA) was constructed by ligating Pseudomonas exotoxin Awith Fc fragment of IgE. However, there was an inevitable problem that the targeted toxins could lead to more serious side effects on patients. Previous wok of our labhas achieved that six kinds of Ig-Fc-PEA targeted toxins with antigenicity attenuatedby weakening the MHC-I-based affinity of targeted toxins Ig-Fc-PEA,and namedthe six targeted toxins Ig-Fc-PEA as TTH, TLH,216VL,140I,140LV and140LVI,respectively, besides, the antigenicity unweakening of recombinant immunotoxinnamed as PRIH.Researches have showed that there was a mutally reinforcing relationshipbetween tumor and inflammation. Around tumor tissue, a large number of mast cellsproduce a variety pro-inflammatory cytokines, making a large number ofmicrovascular growing around the cancer tissue. The main manifestation ofinflammation is that many microvessels develop around the inflammatory tissues.Therefore, the development of tumors is closely related to the complement betweenmast cells and inflammation. Based on this point, if we inhibit the growth of mastcells around cancer tissue, we could effectively inhibit the inflammation aroundcancer organizations, and even inhibit tumor growth and metastasis. Our methodwould be an promising way for effective treatment of NSCLC.Objective：Based on the six kind of Ig-Fc-PEA recombinant immunotoxins (TTH, TLH,216VL,140LV,140I and140LVI) with their MHC-I affinity attenuated and anuntouched immunotoxin (RPIH), this study aims to investigate the inhibitorypotency of the growth of non-small-cell lung cancer cell by these immunotoxins.Methods:1. The recombinant immunotoxins were expressed in E. coli and purified bychromatography affinity method.2. The inhibitory potency the growth of HMC-1and A-549by recombinantimmunotoxins were investigated through MTT or CCK-8method.3. LDH method was assayed to detect the inhibiting potency of the seven kindsof recombinant immunotoxins against HMC-1and the coculture of HMC-1andA-549, respectively.4. The untutored HMC-1was induced for maturity by sodium butyrate and wasassayed through Methods2and3. Results:1. Ig-Fc-PEA recombinant immunotoxins including TTH, TLH,216VL,140LV,140I,140LVI, and RPIH can effectively inhibit the growth of HMC-1, and theninhibit the growth of A-549.2. There was no difference in the apoptosis potency on HMC-1and its coculturebetween antigenicity attenuated immunotoxins (TTH, TLH,216VL,140LV,140I and140LVI) and the original toxin RPIH.Conclusion:Both The antigenicity attenuated immunotoxins (IgE-Fc-PEA) can effectivelyinhibit the growth of NSCLC cells, as the original toxin RPIH does. |
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