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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 1  |  Page : 15-20

The investigation of epsilon toxin effects on different cancerous cell lines and its synergism effect with methotrexate


1 Department of Biology, Faculty of Sciences, The University of Guilan, Rasht, Iran
2 Department of Biochemistry, School of Biological Sciences, Tarbiat Modares University; National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
3 National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

Correspondence Address:
Sadegh Hasannia
Department of Biochemistry, School of Biological Sciences, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.131338

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Background: The overall goal of this study is to use a bacterial toxin as drug delivery agents for chemotherapy drugs and overcome the development of resistance to these medicines. COR-L105 and MDA-MB 231 which are epithelial-like were used in this study. Cytotoxicity assays were performed by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) as metabolic indicator. The toxin was essential to kill 50% (CT50) and IC 50 value (inhibition growth value) for methotrexate were determined as optical density at 540 nm. Epsilon toxin-loaded PLGA nanoparticles were prepared using non-aqueous technique. Surface morphology, in vitro drug release, and encapsulation efficiency of the nanoparticles was determined. Results: Results confirmed that using non-toxic concentration of epsilon toxin, resistance to cancerous cell decreased significantly, which could be an important result in cancer therapy. The synergistic effect of MTX and epsilon toxin showed that bio toxins can be used as supplement with chemical drugs and increase the effect of chemotherapy. The results illustrated that application of PLGA as drug delivery system due to its controlled release properties was beneficial. Conclusion: These finding proposed that due to the ease of local accessibility of lung tumors with aerosol drug delivery, biotoxins can directly be used with chemotherapy drugs in aerosol form.

Abstract in Chinese

ε-毒素联合甲氨蝶呤对于不同肿瘤细胞株的协同效应影响的研究 背景:此研究的目的是在化疗药物中植入一种药物缓释剂类的细菌毒素以克服(肿瘤细胞的)耐药性。上皮样的COR-L105和MDA-MB 231在本研究中被使用。细胞杀伤试验以3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴化物(MTT)作为新陈代谢指示剂。此毒素需要达到50%细胞死亡率(CT50)以及50%抑制细胞生长值(IC50),以确保甲氨蝶呤必须达到540nm的光密度。用无水技术事先准备好负载了ε-毒素的PLGA纳米粒。这些纳米粒的表观形态、离体药物释放,以及包封率都是稳定的。 结果:研究证实在使用非毒性浓度的ε-毒素后,肿瘤细胞的耐药性显著降低,这对化疗是很重要的。甲氨蝶呤与ε-毒素的协同效应提示了生物毒素可以用来作为化疗药物的补充,以增强化疗的作用。此结果说明了PLGA作为给药系统的应用,由于其长效特性对治疗是有利的。 结论:这些研究结果建议,基于肺癌使用气雾给药方式的局部可达性的便利,生物毒素可以和化疗药一起直接以气雾剂形式应用。 关键词:ε-毒素,甲氨蝶呤,纳米粒,聚乳酸-乙醇酸,增效



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