ABSTRACT
Tumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differentiate into M0, M1 and M2 macrophages and TAMs. TAMs were transfected with pcDNA3.1-GAS5, pcDNA3.1-NC, si-GAS5, si-PTEN or si-Ctrl. A human liver cancer cell line (SMCC-7721) was incubated with the modified TAM supernatant. Quantitative real-time PCR and Western blot were performed to detect gene and protein expression. The cell proliferation and invasion properties of the SMCC-7721 cells were detected by MTT and Transwell assays. GAS5 is up-regulated in M1 macrophages and down-regulated in M2 macrophages and TAMs. GAS5 overexpression promoted M1-like polarization of TAMs and inhibited M2-like polarization of TAMs. Moreover, GAS5 promoted the expression of PTEN in TAMs. PTEN-silenced TAM supernatant treatment promoted cell proliferative and invasive properties of the SMCC-7721 cells and diminished the effect of GAS5-overexpressed TAM supernatant on the cell proliferation and invasion by SMCC-7721 cells. Our results demostrared that GAS5 overexpression inhibited M2-like polarization of TAMs by enhancing PTEN expression, thereby inhibiting cell proliferation and invasion by SMCC-7721 cells. Thus, our results suggest that GAS5 may be a new therapeutic target for HCC treatment.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , PTEN Phosphohydrolase/metabolism , RNA, Long Noncoding/genetics , Carcinoma, Hepatocellular/pathology , Cell Differentiation , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , Leukocytes, Mononuclear/pathology , Liver Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm Metastasis , PTEN Phosphohydrolase/genetics , Tumor-Associated Macrophages/pathology , Up-RegulationABSTRACT
Percutaneous transluminal angioplasty using balloon catheters for Budd-Chiari syndrome (BCS) and transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) have become increasingly accepted as alternative therapeutic modalities. However, few studies have investigated the clinical efficacy of combining percutaneous microwave ablation with angioplasty for patients with BCS complicated by HCC. In the present study, a safe and effective method for treating BCS associated with HCC is presented. Color Doppler ultrasonography, magnetic resonance imaging (MRI), computed tomography (CT), inferior venacavography, hepatic arteriogram and cytological examinations were used for the diagnosis. A KY2000 microwave system with an emission of 915 MHz was also employed for the treatment. Two patients with BCS associated with HCC that were administered different adjuvant drug treatments underwent percutaneous transluminal angioplasty and percutaneous microwave ablation successfully, with no treatment-related complications. Combining angioplasty with percutaneous microwave ablation may represent an alternative method for the treatment of BCS associated with HCC.
