Abstract
The present study aimed to investigate the in vivo inhibitory effect of histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) combined with sorafenib on human hepatocellular carcinoma HCCLM3 cells. The nude mice transplanted with HCCLM3 cells were randomly divided into control, SAHA, sorafenib and SAHA+sorafenib groups. The nude mice in the later 3 groups were intragastrically administrated with SAHA (10 mg·kg-1·day-1), sorafenib (10 mg·kg-1·day-1) and SAHA (10 mg·kg-1·day-1) combined with sorafenib (10 mg·kg-1·day-1), respectively, for successive 20 days. Finally, the inhibition rate of tumor was measured. The expressions of MEK1/2, p-ERK1/2, Cyclin D1, Bcl-2, Bax, p53, MMP-2, MMP-9 and uPA in tumor tissues were determined. Results showed that, compared with SAHA and Sorafenib groups, in SAHA+sorafenib groups the inhibition rate of tumor was significantly increased (P < 0.05), the expression levels of MEK1/2, p-ERK1/2, Cyclin D1, Bcl-2, MMP-2 and MMP-9 and uPA protein in tumor tissues were significantly decreased, respectively (P < 0.05), and the expression levels of Bax and p53 protein were significantly increased, respectively (P < 0.05). In conclusion, compared with single drug, SAHA combined with sorafenib can enhance the inhibitory effects on HCCLM3 xenografts in nude mice.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors around the world, especially in Asia, Africa and southern Europe
Forty modeled nude mice were randomly divided into control, suberoylanilide hydroxamic acid (SAHA), sorafenib and SAHA+sorafenib groups, 10 mice in each group
This study investigated the inhibitory effect of SAHA combined with sorafenib on human HCC HCCLM3 cell xenografts in nude mice
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors around the world, especially in Asia, Africa and southern Europe. HCC has high malignancy and short survival time of patients, and the 5 year survival rate of patients with HCC is about 3%5% (Bruix, Reig, Sherman, 2016). Surgery is the main method for treating HCC. Due to the insidious onset and rapid progress, HCC has no atypical symptom at the early stage. Once HCC occurs, it has already entered the late stage, and has usually lost the chance of radical surgical treatment. The low surgicalresection rate and high recurrence and metastasis rates are the main factors affecting the clinical treatment efficacy of HCC (Koniaris et al, 2011). Liver transplantation and interventional therapy are often used for treating HCC, Braz.
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