Abstract
BackgroundThe metastasis of colorectal cancer frequently tends to liver, which is one of the three leading causes of cancer-related deaths worldwide. Growing evidence showed that aspirin could effectively inhibit liver metastasis of colorectal cancer. However, the potential mechanism has not been fully understood.MethodsMouse splenic vein metastasis assay was used to examine the metastatic ability of colon cancer cells in vivo. And wound healing and transwell assay were applied to detect the metastasis potential of C26 and HCT116 colon cancer cell lines in vitro. RT-PCR and western blotting were used to explore Toll-like receptor 4 (TLR4) expression in colon cancer cell lines. The functions of TLR4 in the migration of the colon cancer cell line were analyzed by infecting cells with lentivirus containing TLR4 siRNA.ResultsWe demonstrated that lipopolysaccharides (LPS) could enhance the metastasis potential of C26 and HCT116 colon cancer cell lines. However, aspirin effectively decreased the metastasis capacity of colon cancer cells in vitro and in vivo. We found that the enhancement of LPS on the migration of colon cancer cells by inducing epithelial-mesenchymal transition (EMT) phenotype demonstrated a TLR4-dependent manner. Aspirin treatment lead to the downregulation of TLR4 on C26 cells which resulted in the decrease of C26 cells migration and EMT phenotype that induced by LPS. Additionally, the inhibitory effect from aspirin on the expression of TLR4 on C26 cells leads to the downregulation of NF-κB.ConclusionThe results of our study indicate that LPS origin from intestinal flora may promote the metastasis of colon cancer to liver and aspirin may inhibit the metastasis of colon cancer by inhibiting the expression of TLR4.
Highlights
The metastasis of colorectal cancer frequently tends to liver, which is one of the three leading causes of cancer-related deaths worldwide
B, compared with control group, LPS (10 μg/ml) could significantly promote the migration and invasion of C26 and HCT116 cells. These results indicated that LPS could enhance the colon cancer cells metastasis potential in vitro
Aspirin pretreatment decreased the metastasis capacity of colon cancer cells induced by LPS We have found that LPS could effectively increase the metastasis of colon cancer cells
Summary
The metastasis of colorectal cancer frequently tends to liver, which is one of the three leading causes of cancer-related deaths worldwide. Growing evidence showed that aspirin could effectively inhibit liver metastasis of colorectal cancer. Colorectal cancer (CRC) is one of the most common malignancies worldwide, which has become a major cause of death in developed countries. The liver is the most common metastasis organ of CRC. Aspirin use is associated with the inhibitory effect of breast, esophageal, lung, stomach, ovarian and colorectal cancer, and aspirin is both a chemopreventive and chemotherapeutic agent for breast and colon cancer [4,5,6,7,8]. A recent report on the chemopreventive effects of aspirin showed that the incidence of colon cancer in was significantly decreased [7].
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