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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
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