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

  • Published online on: September 5, 2014     https://doi.org/10.3892/or.2014.3466
  • Pages: 2023-2030
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

November-2014
Volume 32 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

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