Annexin A2 knockdown inhibits hepatoma cell growth and sensitizes hepatoma cells to 5-fluorouracil by regulating β-catenin and cyclin D1 expression.
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 downregulation 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.
Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China.
Chong
C
Wang
Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Yu
Y
Guo
Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Jing
J
Wang
Clinical Laboratory Center of Molecular Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China.
Zhiqun
Z
Min
D017306:Annexin A2 / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D017306:Annexin A2; D051176:beta Catenin; D019938:Cyclin D1; D005472:Fluorouracil