Abstract
Methods Immunohistochemical staining, sequencing, and genetic analysis of liver cancer tissues were performed. The antitumor efficacy of single-agent or combination treatment was measured by cell counting kit-8 assay and colony formation assays. Their antiproliferative and apoptosis activity is evaluated by cell cycle analyses and wound healing assays. The DNA-related proteins were also measured by Western blotting and immunohistochemical staining. The HepG2 xenograft model was used to detect the effects of lenvatinib-alisertib on the antitumor activity. Results AURKA was found to be upregulated in HCC tissues (77.3%, 17/22). Combined alisertib and lenvatinib treatment significantly enhanced the inhibition of proliferation and migration in HepG2 and Hep3B cell lines compared to single-agent treatments (all Ps < 0.01). Alisertib alone or in combination with lenvatinib demonstrated a significant increase in the percentage of super-G2 cells (lenvatinib 1 μM vs. lenvatinib 1 μM + alisertib 0.1 μM 8.84 ± 0.84 vs. 34.0 ± 1.54, P < 0.001). Discontinuous spindles and missegregated chromosomes in HCC cells treated with alisertib in combination with lenvatinib were observed. We further revealed that combined treatment inhibited the expression of DNA damage pathway proteins compared to those of single-agent treatments. In nude mice, combined administration of alisertib combined with lenvatinib significantly enhanced the suppression of tumor growth and induced apoptosis (all Ps < 0.01). Conclusions Our findings provide evidence for the possible use of alisertib in combination with lenvatinib in the treatment of HCC for better therapeutic outcomes.
Highlights
Hepatocellular carcinoma (HCC), which constitutes 90% of primary liver malignancies, is deadly cancer with a rising global burden
By analyzed targeted next-generation sequencing panel captured mutations in coding regions, we found the correlation between the expression of aurora A kinase (AURKA) and mutations in 450 cancer-related genes in hepatocellular carcinoma (HCC) samples
TP53 mutations were detected in 47% of the samples, along with 2 genes, KMT2C and ARID1A with greater than 20% mutation rates, and 7 other genes, STK11, LRP1B, KRAS, CTNNB1, SPTA1, SETD8, and ATM with over 10% mutation rates, including (Figure 1(c))
Summary
Hepatocellular carcinoma (HCC), which constitutes 90% of primary liver malignancies, is deadly cancer with a rising global burden. Marasco et al assessed the performance of several prognostic scores They reported poor performance outcomes of HCC patients treated with sorafenib [4]. The antitumor efficacy of single-agent or combination treatment was measured by cell counting kit-8 assay and colony formation assays. Their antiproliferative and apoptosis activity is evaluated by cell cycle analyses and wound healing assays. Combined alisertib and lenvatinib treatment significantly enhanced the inhibition of proliferation and migration in HepG2 and Hep3B cell lines compared to single-agent treatments (all Ps < 0:01). Our findings provide evidence for the possible use of alisertib in combination with lenvatinib in the treatment of HCC for better therapeutic outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
