Tumor Biology

, Volume 36, Issue 1, pp 303–313 | Cite as

Re-sensitization of 5-FU resistance by SPARC through negative regulation of glucose metabolism in hepatocellular carcinoma

  • Hong-Wei Hua
  • Feng Jiang
  • Qian Huang
  • Zhi-Jun Liao
  • Gang DingEmail author
Research Article


Secreted protein, acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, is implicated in the progression of many cancers. Currently, there is growing evidence for important functions of SPARC in a variety of cancers and its role in cancer depends on tumor types. In this study, we reported SPARC negatively regulated glucose metabolism in hepatocellular carcinoma (HCC). Overexpression of SPARC inhibited glucose uptake and lactate product through downregulation of key enzymes of glucose metabolism. On the other hand, knock down of SPARC reversed the phenotypes. Meanwhile, exogenous expression of SPARC in HepG2 cells resulted in tolerance to low glucose and was correlated with AMPK pathway. Interestingly, the 5-fluorouracil (5-FU)-resistant HepG2 cells showed increased glucose metabolism and downregulated SPARC levels. Finally, we reported the overexpression of SPARC re-sensitize 5-FU-resistant cells to 5-FU through inhibition of glycolysis both in vitro and in vivo. Our study proposed a novel function of SPARC in the regulation of glucose metabolism in hepatocellular carcinoma and will facilitate the development of therapeutic strategies for the treatments of liver tumor patients.


SPARC 5-FU Glucose metabolism Hepatocellular carcinoma Re-sensitization 



This study was supported by Science and Technology Commission of Shanghai Municipality (12411960600), Key Project of Shanghai Municipal Commission of Health and Family Planning (ZK2012A06) and Talents Project of Shanghai Municipal Commission of Health and Family Planning (XBR2013089).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Hong-Wei Hua
    • 1
  • Feng Jiang
    • 2
  • Qian Huang
    • 2
  • Zhi-Jun Liao
    • 2
  • Gang Ding
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of OncologyXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Department of OncologyChongming Branch of Xinhua Hospital Shanghai Jiaotong University School of MedicineShanghaiChina
  3. 3.Institute of Cancer Pain transformationShanghaiChina

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