Liposomal clodronate combined with Cisplatin or Sorafenib inhibits hepatocellular carcinoma cell proliferation, migration and invasion by suppressing FOXQ1 expression

Yilong Zhou,Chunyang Ma,Feng Zhang,Bingfeng Shao,Yuan Chen

doi:10.14715/cmb/2019.66.1.8

Yilong Zhou, Chunyang Ma + Show 3 more

Open Access

https://doi.org/10.14715/cmb/2019.66.1.8

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Abstract

The purpose of this study was to investigate the effect of liposomal clodronate combined with Cisplatin or Sorafenib on the FOXQ1 expression and biological function of hepatocellular carcinoma cell lines. The expression of FOXQ1 was determined in normal hepatic cell line and hepatocellular carcinoma cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). HepG2 and MHCC97H cells were administered low, medium and high concentrations of cisplatin (3, 5 and 7 μg/ml) or Sorafenib (2, 7 and 20 μg/ml) in combination with liposomal clodronate (LC, 20μg/ml), and the expression of FOXQ1 in each group was determined. Cell migration, MTT and transwell assays were used to determine the effects of the treatments on biological functions of HepG2 and MHCC97H cells. qRT-PCR showed that the expression of FOXQ1 mRNA was higher in the four hepatocellular carcinoma cell lines than in normal cells, and the expression of FOXQ1 mRNA in HepG2 and MHCC97H cells were more dominant. All the tested doses of Cisplatin, but only high dose Sorafenib down-regulated the expression of FOXQ1. However, Sorafenib at low and medium concentrations had no significant effect on the expression of FOXQ1. When Cisplatin or Sorafenib was administered in combination with LC, the expression level of FOXQ1 was significantly reduced. Cell migration, MTT and transwell assays showed that proliferation, migration and invasion were inhibited when each drug was administered alone, but was stronger when the drugs were combined with liposomal clodronate.Liposomal clodronate combined with Cisplatin or Sorafenib down-regulates the expression of FOXQ1 in HepG2 and MHCC97H hepatoma cells, and inhibits their proliferation, migration and invasion.

Highlights

Hepatocellular carcinoma (HCC) is a frequently-occurring malignant tumor affecting human health due to its poor prognosis and poor clinical response to traditional chemotherapy and radiotherapy [1]
MTT and transwell assays were used to determine the effects of the treatments on biological functions of HepG2 and MHCC97H cells. quantitative real-time polymerase chain reaction (qRT-PCR) showed that the expression of foxhead box protein Q1 (FOXQ1) mRNA was higher in the four hepatocellular carcinoma cell lines than in normal cells, and the expression of FOXQ1 mRNA in HepG2 and MHCC97H cells were more dominant
Expression levels of FOXQ1 in different cell lines Results from qRT-PCR showed that the expression of FOXQ1 in LO2 cell line was significantly lower than those in hepatocellular carcinoma cells (HepG2, MHCC97L, SMMC-7721 and MHCC97H) (p

Summary

Introduction

Hepatocellular carcinoma (HCC) is a frequently-occurring malignant tumor affecting human health due to its poor prognosis and poor clinical response to traditional chemotherapy and radiotherapy [1]. Its mortality ranks third in the world, and second in cancer mortality in Asia [2]. Factors involved in the etiology of HCC are yet to be unraveled [3]. Hepatitis B and hepatitis C may be major predisposing factors for HCC [4]. Some strategies used for improving the lives of HCC subjects include liver transplant surgery and chemotherapy. The prognosis of HCC still remains unimpressive due to drug resistance and high metastatic rates of HCC [5]. There is need for development of more effective treatment strategies for HCC

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