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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 4 > Sen Lu, Yun Gao, Xinli Huang and Xuehao Wang 

Cantharidin Exerts Anti-Hepatocellular Carcinoma by Mir-214 Modulating Macrophage Polarization

Sen Lu, Yun Gao, Xinli Huang and Xuehao Wang 
Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing 210029, China.  Corresponding author: Xuehao Wang, Mailing address: Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Address: 300 Guangzhou Rd., Nanjing 210029, People’s Republic of China. Tel: 86-25-83718836ext6476 Email: wangxh@njmu.edu.cn.
Abstract :

Norcantharidin (NCTD), a demethylated form of cantharidin, has been used as a routine anticancer drug in China. In this study, the effect and mechanism of NCTD on anti-hepatocellular carcinoma (HCC) was examined. In vivo antitumor activity was investigated in hepatoma-bearing mice by intraperitoneal injection of different concentration of NCTD. The levels of MicroRNAs (miRNAs) and mRNA were detected by real-time PCR. The concentrations of IL-10 and IL-12 in BMDMs, Raw 264.7 cells or tumor-associated macrophages (TAMs) were measured with ELISA kit. The effects of TAMs on H22 cell survival and invasion were assayed via the CCK-8 and tumor invasion assay, respectively. Anti-miR-214 or pre-miR-214 was used to down-regulate or up-regulated miR-214 expression. The results showed that NCTD drastically impaired tumor growth in hepatoma-bearing mice, correlating with increased anti-tumor activity of TAMs. Moreover, NCTD stimulation led to an alteration of HCC microenvironment, reflected by a decrease in a shift from M2 to M1 polarization and the populations of CD4+/CD25+Foxp3 T cells. The activation of STAT3 was inhibited in TAMs from hepatoma-bearing mice injected with NCTD. Addition of NCTD to treat RAW264.7 or TAMs enhanced M1 polarization through increase of miR-214 expression. NCTD significantly inhibited β-catenin expression, which could be reversed by miR-214 inhibitor. Conditioned media from TAMs in hepatoma-bearing mice treated with NCTD or TAMs transfected with pre-miR-214 inhibited survival and invasion of H22 cells. This finding reveals a novel role for NCTD on inhibition of HCC through miR-214 modulating macrophage polarization. 

Keywords :
Norcantharidin, hepatocellular carcinoma, microenvironment, macrophage polarization, miR-214

Date Deposited : 09 Feb 2016 10:11

Last Modified : 09 Feb 2016 10:11

Official URL: http://www.ijbs.com/v10i4

Volume 10, Number 4, - 2014 , ISSN 1449-2288

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