Mutations in the adenomatous polyposis coli (Apc) tumor suppressor gene represent the primary genetic defect in colon carcinogenesis. Apc+/- mouse models exhibit pre-invasive small intestinal adenomas. Cell culture models exhibiting Apc defects in the colon and quantifiable cancer risk provide a novel clinically relevant approach. The tumor-derived Apc-/- colonic epithelial cell line 1638N COL-Pr1 represented the experimental model. The anti-inflammatory drugs sulindac (SUL) and celecoxib (CLX) represented the test compounds. Compared with non-tumorigenic Apc+/+ C57COL cells, the Apc+/- 1638N COL cells and Apc-/- 1638N COL-Pr1 cells exhibited progressive loss of homeostatic growth control. Compared with Apc+/- cells, Apc-/- cells displayed increased expression of biomarkers specific for hyper-proliferation. Treatment of Apc-/- cells with SUL and CLX resulted in inhibition of anchorage-independent colony formation in vitro, which is indicative of reduced cancer risk in vivo. Mechanistically, SUL and CLX suppressed the expression of the Apc target genes β-catenin, cyclin D1, c-Myc and cyclooxygenase-2. Long-term treatment with high concentrations of SUL and CLX led to the selection of hyper-proliferative drug-resistant phenotypes. The Apc-/- SUL-resistant phenotype displayed spheroid formation and enhanced the expression of the stem cell-specific molecular markers CD44, CD133 and c-Myc. These data demonstrated the growth-inhibitory efficacy of SUL and CLX and indicated that drug resistance leads to the selection of a putative cancer stem cell phenotype. The study outcome validates a stem cell-targeted mechanistic approach to identify testable alternative leads for chemotherapy-resistant colon cancer.Keywords: anti-inflammatory drugs; colonic epithelium; stem cells.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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