Annexin A2 knockdown inhibits hepatoma cell growth and sensitizes hepatoma cells to 5.pdfVIP

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Annexin A2 knockdown inhibits hepatoma cell growth and sensitizes hepatoma cells to 5.pdf

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Annexin A2 knockdown inhibits hepatoma cell growth and sensitizes hepatoma cells to 5

MOLECULAR MEDICINE REPORTS 11: 2147-2152, 2015 Abstract. Hepatocellular carcinoma (HCC) is one of the most common cancer types, and chemotherapy plays an important role in treatment of HCC. However, long-term treatment with chemotherapeutic drugs such as 5?fluorouracil (5-FU) often results in chemoresistance, and the underlying mechanisms remain unclear. In this study, we showed that the annexin A2 (ANXA2) protein is highly expressed in hepatoma cells compared to healthy cells. Knockdown of the ANXA2 gene inhibited hepatoma cell growth, and the underlying mechanism may involve cell cycle inhibition through down- regulation of β-catenin and cyclin D1. We also investigated the role of ANXA2 in chemotherapeutic treatment with 5-FU. 5-FU inhibited hepatoma cell growth, while ANXA2 overexpression reduced, and knockdown enhanced, the effects of 5-FU on hepatoma cell growth. Furthermore, β-catenin and cyclin D1 were asscociated with the ANXA2-induced resistance. Taken together, our data suggest that the ANXA2 protein is a critical factor in HCC and that its downregulation can enhance chemotherapeutic treatment with 5-FU. ANXA2 may thus constitute a new therapeutic target for HCC. Introduction Hepatocellular carcinoma (HCC) is one of the most common cancer types worldwide and has an extremely poor prog- nosis (1,2). Certain risk factors, such as chronic hepatitis B and C virus infections, exposure to aflatoxin, non?alcoholic fatty liver disease and diabetes, contribute to HCC development. Although the etiology of HCC is well documented, the ability to treat HCC remains limited. Chemotherapy is commonly used in treatment of HCC. 5-Fluorouracil (5-FU) has been used to treat various cancer types, and is considered as a first?line anticancer drug for HCC chemotherapy worldwide. Unfortunately, its use is limited, since long-term treatment with this drug often results in chemoresistance, and the underlying mechanisms remain unclear (3,4). Therefore