Journal of Clinical & Experimental Pathology
Open Access

Abstract

The role of TLRs in tumor growth is paradoxical. In colon cancer, APC/GSK-3β/β-catenin pathway cross regulates TLRs/NF- Î?b pathway through β-catenin, and possibly associated with APC genotype. It is speculated that the connection between TLRs and APC/GSK-3b/ β-Catenin may relate with APC gene mutation. This study aims to investigate the mechanism of TLRs/ NF-κB pathway activation in different APC status in colon cancer. SiRNA transiently targeting APC was transfected into human HCT116 cell with wild APC, while ShRNA-APC was stably transfected into HCT116 and human normal colon cell line NCM460 with lentiviral packaging system. Cell lines with different APC status were stimulated with LPS (lipopolysaccharide, TLR4 agonist). SKID xenograft models of HCT116 and HCT116-ShAPC cells were established, followed by intra tumoral injection of LPS (5μg, 10 μg, 20μg). p-β-catenin, NF-κB, p-NF-κB and caspase-3 expression in tumor tissues were tested with Western blot and immunohistochemistry. Cells proliferation of HCT116-SiAPC and HCT116-ShAPC treated with LPS increased similar to HT29 and SW480 with APC mutation, while proliferation of HCT116 cells was inhibited. Activation of TLRs/NF-Î?B signaling pathway by LPS was different between wild and mutated APC cell lines. Our data indicated that changes of APC phenotype produced different biological behavior by regulating the levels of β- Catenin.

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