Abstract
Colon cancer is one of the deadliest tumors in the world, and with high metastasis rate and mortality, effective drugs for its treatment are still in need. Auranofin (AF) is a gold complex that has been attested by FDA for treating human rheumatism, and researchers have found that AF acts as a great antitumor drug in recent years. ICG-001 is a small molecule inhibitor of Wnt/β-catenin pathway. In the present study, we aimed to explore the synergistic antitumor effects and the underlying mechanisms of AF and ICG-001 combination therapy on human colon cancer. The results showed that AF and ICG-001 synergistically depressed the growth and invasion of human colon cancer cells by inhibiting the phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) and its downstream mediator B-cell lymphoma-2-like 1 (Bcl-xL) and inducing caspase-3-dependent apoptosis. Moreover, AF combined with ICG-001 synergistically inhibited the growth of colon cancer in subcutaneous xenograft mice models and restrained metastasis in lung metastasis mice models. In conclusion, our results demonstrated that combination of AF and ICG-001 suppressed the proliferation and metastasis of colon cancer by inhibiting STAT3 phosphorylation. Therefore, this combination therapy may possess potential therapeutic properties for human colon cancer.
Highlights
Colon cancer is one of the deadliest tumor in the world, with high metastasis rate and mortality [1]
We found that AF and ICG-001 synergistically depressed the growth and metastasis of human colon cancer in vitro and in vivo
According to the cell viability assay, AF and ICG-001 both suppressed the proliferation of colon cancer cell lines
Summary
Colon cancer is one of the deadliest tumor in the world, with high metastasis rate and mortality [1]. Surgery is the most common treatment for patients with early-stage colon cancer, chemotherapy and target drugs are still necessary for those with advanced-stage and metastasis cancer. According to the statistics of United States, the 5-year survival rates for patients with colon cancer from 2001~2003 to 2004~2009 increase only by 0.9% (from 63.7 to 64.6%) [2], and the 5-year relative survival rate for those patients is 64% until year 2019 [3], indicating that the novel therapy for colon cancer is still under urgent need. Combination therapy is using multiple drugs for treating diseases and reducing suffering. Drug combinations have been widely used and become the leading choice for treating the most dreadful diseases, such as cancer and infectious diseases [4]
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