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Targeted cancer therapy based on blocking the expression of genes and small doses of oxaliplatin.
Poster Title: Targeted cancer therapy based on blocking the expression of genes and small doses of oxaliplatin.
Submitted on 01 Apr 2014
Author(s): Bavykin A.S.1, Korotaeva A.A.1, Poyarkov S.V.2, Syrtsev A.V.1, Karpukhin A.V.1
Affiliations: 1. Centre for Medical Genetics Russian Academy of Medical Sciences Moskvorechie Str. 1, Moscow 115478, 2. Koltsov Institute of Developmental Biology Russian Academy of Sciences, Vavilov Str. 26, Moscow 119334
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Poster Information
Abstract: Results. We found that colon cancer cells HCT-116, when exposed to low concentrations of oxaliplatin (5 and 10mkM) showed the the same survival rate as for the untreated cells, however their expression patterns were different. We examined the panel of genes with various functions in the presence of small dozes of oxaliplatin and picked up those, that displayed marked overexpression and were depended both on the oxaliplatin dose escalation and the incubation period. These genes belong to the family of inhibitors of apoptosis and associated with the caspase cascade. Shutting down the expression of these genes was performed using short interfering RNAs (siRNAs), attached to the liposome particles. These ultra – small molecules can suppress synthesis of desired proteins at the level of messenger RNA of Birc3 and Birc7 genes. Due to the ultra small size, and low concentration, that is sufficient enough to inhibit protein synthesis at an early stage. Thus siRNA have considerable advantages compared with targeted antibodies.
Conclusion. Identified target genes Birc3 and Birc7 display specific response to oxaliplatin treatment. Joint inhibiting the synthesis of these genes resulted in virtually complete (85%, p<0,05) suppression of the viability of cancer cells and increased (7-fold) sensitivity of cancer cells to low doses of oxaliplatin.
Summary: The major drawbacks of the prescribed chemotherapy, are still remain the significant side effects and drug - resistance. Even targeted chemotherapy by means of specific antibodies do not always help to solve these complications. Our purpose was to identify potential biological targets associated with the development of drug resistance and to develop a specific method of suppressing the viability of cancer cells exposed to low doses of standard chemotherapy.References: 1.) Yang D, Song X, Zhang J, et al. Therapeutic potential of siRNA-mediated combined knockdown of the IAP genes (LIVIN, XIAP, and Survivin) on human bladder cancer T24 cells. Acta Biochim Biophys Sin (Shanghai) 2010;42(2):137–144.
2.) Oh BY, Lee RA, Kim KH. siRNA targeting LIVIN decreases tumor in a xenograft model for colon cancer. World J Gastroenterol. 2011;17(20):2563–2571.
3.) Bavykin A.S., Korotaeva AA., Syrtsev, Karpukhin A. V., Tulyandin S.A. The development the effectiveness of
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