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Abstract
Abstract Metastatic colorectal cancer remains a serious health concern with poor patient survival. 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX), the standard therapy for colorectal cancer, has met with limited success. Recurrence of the tumor after chemotherapy could partly be explained by the enrichment of the chemo-resistant sub-population of cancer stem cells (CSCs) that possess the ability for self-renewal and differentiation into different lineages in the tumor. Therefore development of therapeutic strategy that target CSCs is highly desirable in reducing the risk of relapse and metastasis. The current investigation was undertaken to examine the effectiveness of the combination therapy of dasatinib (a Src inhibitor) and curcumin (a dietary ingredient) in inhibiting the growth and other properties of carcinogenesis of chemo-resistant colon cancer cells that are enriched in CSCs. Human colon cancer cells HCT-116 (p53 wild type; K-ras mutant) and HT-29 (p53 mutant; K-ras wild type) were used to generate FOLFOX resistant {referred to as chemoresistant (CR)} cells. The CR cells showed higher expression of CSCs markers, cell invasion potential and ability to form colonospheres, compared to the corresponding parental cells. The combination therapy of dasatinib and curcumin demonstrated synergistic interactions in CR-HCT-116 and CR-HT-29 cells. This caused inhibition of cellular growth, invasion and colonosphere formation and reduction in CSC population as evidenced by decreased expression of CSC specific markers: CD133, CD44, CD166 and ALDH. In conclusion, we propose that the combination therapy of dasatinib and curcumin may be an effective therapeutic strategy for re-emergence of chemo-resistant colon cancer by targeting CSC sub-population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3503. doi:10.1158/1538-7445.AM2011-3503
Published Version
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