Aurora-a inhibitor synergistically enhances the inhibitory effect of anlotinib on hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide. Except for all guidelines that have been approached in clinic, anlotinib and Aurora-A inhibitors also have been proved to be effective in HCC. However, Anlotinib which is a member of anti-angiogenesis therapy, has achieved great benefits in clinical trials, but its single-agent treatment limitations are also very obvious like drug resistance. Aurora-A inhibitors are in clinical trials but has limited benefit. Combination therapy is clearly superior to monotherapy under the situation. So we hope to explore whether the combination of the two drugs can enhance their strengths and avoid their weaknesses to obtain more clinical benefits. We confirmed that alisertib and anlotinib had an inhibitory effect on HCC cells in a time-dose relationship at first. In vitro, cytological experiments showed that the combination of the two drugs had a synergistic effect on inhibiting cell proliferation, invasion, and metastasis, and promoting cell apoptosis. We also uncovered the underlying molecular mechanism by which the combination of Aurora-A inhibitor alisertib and anlotinib inhibited HCC by inhibiting the activation of the NF-ĸB signaling pathway. In a word, we have demonstrated that anlotinib combined with Aurora-A inhibitor is effective, which also broadens the horizon for anlotinib before officially enter the clinical treatment of HCC in the future.