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Article

Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts

  • Authors:
    • Fanjie Meng
    • Bin Cao
    • Zengli Feng
    • Shunmao Ma
    • Haigang Wang
    • Yanshu Li
    • Hui Li
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, North-China Oil Field General Hospital, Hebei Medical University, Renqiu 062552, P.R. China, Department of General Surgery, North-China Oil Field General Hospital, Hebei Medical University, Renqiu 062552, P.R. China
  • Pages: 2023-2030
    |
    Published online on: September 5, 2014
       https://doi.org/10.3892/or.2014.3466
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Abstract

Ras mutations contribute to human cancer development. The present study assessed the Ras V12 mutation in hepatocellular carcinoma (HCC) cells and the role of its silencing in vitro and in nude mouse xenografts. HCC BEL7402 cells expressed mutations of V12 (Val/Gly) and wild-type H-Ras, whereas SMMC7721 cells only expressed wild-type H-Ras. The shRNA constructs specifically silenced mutated H-Ras expression in BEL7402 cells, but did not affect wild-type Ras expression in SMMC7721 cells. Silencing of mutated H-Ras expression reduced BEL7402 cell viability, induced apoptosis and arrested cells at the G0/G1 phase of the cell cycle. Expression of phospho-Akt was also significantly decreased, while several apoptotic proteins were also activated. Furthermore, sensitivity of stably H1-shRNA and H2-shRNA transfected BEL7402 cells to cisplatin treatment was increased by 7.19- and 5.39-fold, respectively, compared to that in the negative control cells, and apoptosis-related gene expression was also altered. Intraperitoneal administration of cisplatin led to a substantial reduction in HCC xenograft growth by 81 and 77% in the H1-shRNA and H2-shRNA transfected tumor xenografts, respectively, compared to a 37% reduction in mice bearing negative control tumor cells. These data demonstrate that knockdown of mutated H-Ras V12 expression induced chemosensitivity of HCC cells to cisplatin treatment in vitro and in vivo.
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Copy and paste a formatted citation
Spandidos Publications style
Meng F, Cao B, Feng Z, Ma S, Wang H, Li Y and Li H: Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts. Oncol Rep 32: 2023-2030, 2014.
APA
Meng, F., Cao, B., Feng, Z., Ma, S., Wang, H., Li, Y., & Li, H. (2014). Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts. Oncology Reports, 32, 2023-2030. https://doi.org/10.3892/or.2014.3466
MLA
Meng, F., Cao, B., Feng, Z., Ma, S., Wang, H., Li, Y., Li, H."Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts". Oncology Reports 32.5 (2014): 2023-2030.
Chicago
Meng, F., Cao, B., Feng, Z., Ma, S., Wang, H., Li, Y., Li, H."Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts". Oncology Reports 32, no. 5 (2014): 2023-2030. https://doi.org/10.3892/or.2014.3466
Copy and paste a formatted citation
x
Spandidos Publications style
Meng F, Cao B, Feng Z, Ma S, Wang H, Li Y and Li H: Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts. Oncol Rep 32: 2023-2030, 2014.
APA
Meng, F., Cao, B., Feng, Z., Ma, S., Wang, H., Li, Y., & Li, H. (2014). Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts. Oncology Reports, 32, 2023-2030. https://doi.org/10.3892/or.2014.3466
MLA
Meng, F., Cao, B., Feng, Z., Ma, S., Wang, H., Li, Y., Li, H."Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts". Oncology Reports 32.5 (2014): 2023-2030.
Chicago
Meng, F., Cao, B., Feng, Z., Ma, S., Wang, H., Li, Y., Li, H."Knockdown of mutated H-Ras V12 expression induces chemosensitivity of hepatocellular carcinoma cells to cisplatin treatment in vitro and in nude mouse xenografts". Oncology Reports 32, no. 5 (2014): 2023-2030. https://doi.org/10.3892/or.2014.3466
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