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Sorafenib sensitizes hepatocellular carcinoma cell to cisplatin via suppression of Wnt/β-catenin signaling

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In this study, we found that nuclear accumulation of β-catenin was higher in cisplatin-resistant Huh7 cells than in Huh7 cells, indicating that Wnt signaling was activated in cisplatin-resistant cells. Wnt signaling inhibition increased cisplatin-induced growth inhibition in hepatoma cell. We further demonstrated that sorafenib could inhibit Wnt signaling in Huh7 cells and cisplatin-resistant Huh7 cells. Co-treatment with cisplatin and sorafenib was more effective in inhibiting cancer cell proliferation than cisplatin alone in vitro and in vivo, whereas Wnt3a (Wnt activator) treatment abrogated sorafenib-induced growth inhibition. These data demonstrated that sorafenib sensitizes human HCC cell to cisplatin via suppression of Wnt/β-catenin signaling, thus offering a new target for chemotherapy of HCC.

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Authors and Affiliations

  1. The Fifth Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China

    Yongpeng Wei, Zhouchong Wang, Guangshun Yang, Ning Yang & Junhua Lu

  2. The Second Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China

    Ningjia Shen, Bin Yi & Yinghe Qiu

Authors
  1. Yongpeng Wei
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  2. Ningjia Shen
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  3. Zhouchong Wang
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  4. Guangshun Yang
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  5. Bin Yi
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  6. Ning Yang
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  7. Yinghe Qiu
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  8. Junhua Lu
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Corresponding authors

Correspondence to Yinghe Qiu or Junhua Lu.

Additional information

Yongpeng Wei, Ningjia Shen, and Zhouchong Wang contributed equally to this study.

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Wei, Y., Shen, N., Wang, Z. et al. Sorafenib sensitizes hepatocellular carcinoma cell to cisplatin via suppression of Wnt/β-catenin signaling. Mol Cell Biochem 381, 139–144 (2013). https://doi.org/10.1007/s11010-013-1695-6

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  • DOI: https://doi.org/10.1007/s11010-013-1695-6

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