ИСТИНА

Overexpression of apoptosis inhibitors is considered to be one of the main causative factor of apoptosis reduction and drug resistance of colorectal cancers. We set up a profile analysis of a number of genes related to apoptosis inhibition and cell proliferation in the colon cancer line HT-29: c-IAP-2, cIAP-3, XIAP, Survivin, Livin, FLIP, HspA5, Gstp1, Bcl2, c-myc, caspase 8, TRAP-1, Bcl2L, Kras. The analysis has revealed at high level the expression of TRAP-1, Survivin, XIAP and FLIP. The oncogene Kras was found to be expressed even stronger compared with TRAP-1 or Survivin. Most of tumors contain mutant allele Kras in the 2-nd exon. However no Kras mutation was found, arising a question of gene’s hyperactivation in these cells. As far as cancer cell proliferation is dependent on Kras expression, we performed silencing by means of anti-Kras-siRNA. 38% of cell apoptosis was a result of this inhibition. The double decrease of cell viability (63%) was observed when used a combination of anti-Kras, Survivin, FLIP siRNAs. It is interesting that additive effect of three siRNA action was observed. This effect may serve for a good treatment strategy to induce apoptosis of colon tumor cells.