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Article

Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo

  • Authors:
    • Wei Zhang
    • Songyang Liu
    • Kai Liu
    • Bai  Ji
    • Yingchao Wang
    • Yahui Liu
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
  • Pages: 1913-1922
    |
    Published online on: August 19, 2014
       https://doi.org/10.3892/or.2014.3418
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Abstract

Sorafenib (SOR), a vascular endothelial growth factor receptor (VEGFR) inhibitor, is in wide clinical use for the treatment and prevention of liver cancer. However, extended SOR administration for hepatocellular carcinoma (HCC) induces drug resistance thereby limiting its efficacy and highlighting the need for improved therapeutic strategies. It has previously been demonstrated that knockout of a disintegrin and metalloproteinase 10 (ADAM10) via siRNA induced cancer apoptosis and decreased chemotherapy drug resistance. However, whether knockout of ADAM10 is able to decrease SOR resistance remains to be determined. Therefore, in the present study, the effect of siRNA-ADAM10 in combination with SOR was analyzed in HCC cell lines (HepG2) by inhibiting tumor growth and simultaneously reducing doses of SOR. Cell proliferation, apoptosis, migration, invasion and involvement in receptor signaling were determined after siRNA-ADAM10 was applied in combination with SOR treatment. Tumor growth ability in nude mice was also detected. The results showed that siRNA-ADAM10 in combination with SOR treatment in HCC cancer cells significantly suppressed proliferation, migration and invasion, and induced tumor apoptosis in vitro, and suppressed tumor growth in vivo. In addition, the results showed that knockout of ADAM10 by siRNA inhibited the constitutive phosphorylation of PI3K and AKT, which may contribute to the reduction of SOR resistance. Collectively, our experimental results indicate that knockout of ADAM10 by siRNA increased the SOR antitumor activity of liver cancer in vitro and in vivo, and that this additive combination is a promising drug candidate for treatment of HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Liu S, Liu K, Ji B, Wang Y and Liu Y: Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo. Oncol Rep 32: 1913-1922, 2014.
APA
Zhang, W., Liu, S., Liu, K., Ji, B., Wang, Y., & Liu, Y. (2014). Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo. Oncology Reports, 32, 1913-1922. https://doi.org/10.3892/or.2014.3418
MLA
Zhang, W., Liu, S., Liu, K., Ji, B., Wang, Y., Liu, Y."Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo". Oncology Reports 32.5 (2014): 1913-1922.
Chicago
Zhang, W., Liu, S., Liu, K., Ji, B., Wang, Y., Liu, Y."Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo". Oncology Reports 32, no. 5 (2014): 1913-1922. https://doi.org/10.3892/or.2014.3418
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Liu S, Liu K, Ji B, Wang Y and Liu Y: Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo. Oncol Rep 32: 1913-1922, 2014.
APA
Zhang, W., Liu, S., Liu, K., Ji, B., Wang, Y., & Liu, Y. (2014). Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo. Oncology Reports, 32, 1913-1922. https://doi.org/10.3892/or.2014.3418
MLA
Zhang, W., Liu, S., Liu, K., Ji, B., Wang, Y., Liu, Y."Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo". Oncology Reports 32.5 (2014): 1913-1922.
Chicago
Zhang, W., Liu, S., Liu, K., Ji, B., Wang, Y., Liu, Y."Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo". Oncology Reports 32, no. 5 (2014): 1913-1922. https://doi.org/10.3892/or.2014.3418
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