Abstract
Abstract
Survivin is a novel member of the IAP family of proteins with a potential dual role in apoptosis inhibition and regulation of mitosis. In addition, survivin is implicated in the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis, and chemoresistance. Survivin is up-regulated in almost all cancers, including colon cancer, but has low or no expression in most normal, differentiated adult tissues. Expression of survivin in cancer cells has been shown to promote tumorigenesis. Besides, the expression levels of survivin strongly correlate with the proliferative activity of the tumours indicating a possible role in cell cycle regulation and cancer progression.
However, the effect of a novel chemotherapy such as oxaliplatin and vinflunine on survivin expression has been not well characterized yet. Therefore, the effects of oxaliplatin and vinflunine treatment on survivin protein expression in lymphocytes from colon cancer patients against healthy volunteers were investigated. Treatment with either oxaliplatin or vinflunine significantly increased the formation of micronuclei with p < 0.01 in dose-dependent manner by using a cytokinesis-block micronucleus (CBMN) assay. In addition, treatment with both compounds increased chromosomal missegregation (p<0.01) as investigated by a combination of the CBMN assay with fluorescence in situ hybridisation (MN-FISH). Survivin protein expression in lymphocytes from colon cancer patients treated with oxaliplatin and vinflunine were evaluated by Western blot assay. The expression of survivin was significantly reduced up to 3-fold and 6-fold in survivin expression in all the concentrations of oxaliplatin and vinflunine tested respectively (p < 0.001).
In conclusion, significant reduction in survivin protein expression was observed in lymphocytes from colon cancer patients exposed to oxaliplatin or vinflunine. Also evidence for mitotic catastrophe has been found for the first time as one plausible mechanism of oxaliplatin and vinflunine induced lymphocyte death. Oxaliplatin and vinflunine effectively induce DNA damage in vitro leading to aneuploidy in human lymphocytes observed in chromosome missegregation during M-phase. Future work will examine the actual impact of DNA damage to improve chemotherapy treatment or open a new approach in cancer therapy.
Citation Format: Amal A. Alotaibi. The decrease of the survivin protein expression induces chromosomal missegregation in colon cancer patients lymphocytes treated with oxaliplatin and vinflunine. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C38. doi:10.1158/1538-7755.DISP13-C38