NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells

  • Authors:
    • Satoshi Furuhashi
    • Hiroki Sugita
    • Hiroshi Takamori
    • Kei Horino
    • Osamu Nakahara
    • Hirohisa Okabe
    • Keisuke Miyake
    • Hiroshi Tanaka
    • Toru Beppu
    • Hideo Baba
  • View Affiliations

  • Published online on: October 24, 2011     https://doi.org/10.3892/ijo.2011.1243
  • Pages: 807-815
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Abstract

Nitric oxide (NO) shows tumoricidal activity. We had previously reported that NO downregulates the phosphatidylinositol-3-kinase/Akt pathway, but upregulates the MEK/ERK pathway downstream of growth factor signaling. We hypothesized that NO donor and MEK inhibitor in combination synergistically inhibit the viability of cancer cells compared to either NO donor or MEK inhibitor alone. We determined the effects of S-nitrosoglutathione (GSNO, NO-donor) and U0126 (MEK inhibitor) on insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) signaling, proliferation and invasion in cancer cell lines. GSNO inhibits phosphorylation of IGF-I receptor (IGF-IR), EGF receptor (EGFR) and Akt, but upregulates ERK1/2 phosphorylation in MIAPaCa-2 and HCT-116 cells after stimulation by IGF-I and EGF. On the other hand, U0126 inhibits phosphorylation of ERK1/2, but upregulates phosphorylation of IGF-IR and EGFR in MIAPaCa-2 and HCT-116 cells. The combination of GSNO and U0126 downregulates phosphorylation of IGF-IR, EGFR, Akt and ERK1/2 after stimulation by IGF-I and EGF. GSNO as well as U0126, inhibits the proliferation of MIAPaCa-2, HCT-116, Panc-1, MCF-7, HT-29 and AGS cells in a dose-dependent manner. GSNO and U0126 in combination synergistically inhibit proliferation and invasion of cancer cells. These results indicate that the combined treatment of NO donor and MEK inhibitor may be promising in cancer therapy.

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March 2012
Volume 40 Issue 3

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Spandidos Publications style
Furuhashi S, Sugita H, Takamori H, Horino K, Nakahara O, Okabe H, Miyake K, Tanaka H, Beppu T, Baba H, Baba H, et al: NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells. Int J Oncol 40: 807-815, 2012.
APA
Furuhashi, S., Sugita, H., Takamori, H., Horino, K., Nakahara, O., Okabe, H. ... Baba, H. (2012). NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells. International Journal of Oncology, 40, 807-815. https://doi.org/10.3892/ijo.2011.1243
MLA
Furuhashi, S., Sugita, H., Takamori, H., Horino, K., Nakahara, O., Okabe, H., Miyake, K., Tanaka, H., Beppu, T., Baba, H."NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells". International Journal of Oncology 40.3 (2012): 807-815.
Chicago
Furuhashi, S., Sugita, H., Takamori, H., Horino, K., Nakahara, O., Okabe, H., Miyake, K., Tanaka, H., Beppu, T., Baba, H."NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells". International Journal of Oncology 40, no. 3 (2012): 807-815. https://doi.org/10.3892/ijo.2011.1243