Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and these signal pathways are amplified in cisplatin-resistant squamous cell carcinoma

  • Authors:
    • Kenta Aoki
    • Tetsuya Ogawa
    • Yatsuji Ito
    • Shigeru Nakashima
  • View Affiliations

  • Published online on: February 1, 2004     https://doi.org/10.3892/or.11.2.375
  • Pages: 375-379
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Abstract

cis-Diaminodichloroplatinum (II) (cisplatin) is one of the most effective anticancer drugs and is widely used for the treatment of squamous cell carcinoma (SCC). However, its efficacy is often limited due to the development of resistance. Although several factors implicated in cisplatin resistance have been identified, the resistance mechanisms in detail are not fully understood yet. In the present study, we have examined the implication of survival signaling pathways in cisplatin-resistance. Cisplatin induced activation of Ras and its downstream effector kinases, Raf/MEK/ERK in UM-SCC-23 human squamous cell carcinoma, suggesting that this anticancer drug activates survival signal pathway in addition to apoptosis signals. In cisplatin-resistant UM-SCC-23 in culture, which we have established, the protein levels of Ras, Raf-1 and MEK were drastically elevated compared to parent UM-SCC-23, and ERK and Akt signals were constitutively activated. U0126, an inhibitor for MEK and LY294002, an inhibitor for phosphatidylinositol 3-kinase (PI3K), sensitized resistant UM-SCC-23 to cisplatin-induced cell death. These results indicate that Raf/MEK/ERK and PI3K/Akt signal cascades may play a considerable role in cisplatin resistance in SCC.

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February 2004
Volume 11 Issue 2

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

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Spandidos Publications style
Aoki K, Ogawa T, Ito Y and Nakashima S: Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and these signal pathways are amplified in cisplatin-resistant squamous cell carcinoma. Oncol Rep 11: 375-379, 2004
APA
Aoki, K., Ogawa, T., Ito, Y., & Nakashima, S. (2004). Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and these signal pathways are amplified in cisplatin-resistant squamous cell carcinoma. Oncology Reports, 11, 375-379. https://doi.org/10.3892/or.11.2.375
MLA
Aoki, K., Ogawa, T., Ito, Y., Nakashima, S."Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and these signal pathways are amplified in cisplatin-resistant squamous cell carcinoma". Oncology Reports 11.2 (2004): 375-379.
Chicago
Aoki, K., Ogawa, T., Ito, Y., Nakashima, S."Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and these signal pathways are amplified in cisplatin-resistant squamous cell carcinoma". Oncology Reports 11, no. 2 (2004): 375-379. https://doi.org/10.3892/or.11.2.375