Placenta growth factor induces melanoma resistance to temozolomide through a mechanism that involves the activation of the transcription factor NF-κB

  • Authors:
    • Lauretta Levati
    • Federica Ruffini
    • Alessia Muzi
    • Kazuo Umezawa
    • Grazia Graziani
    • Stefania D'Atri
    • Pedro Miguel Lacal
  • View Affiliations

  • Published online on: January 1, 2011     https://doi.org/10.3892/ijo_00000844
  • Pages: 241-247
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Abstract

Placenta growth factor (PlGF) and its receptor vascular endothelial growth factor receptor-1 (VEGFR-1) are co-expressed in a large number of human melanoma cell lines. Moreover, a correlation between in vivo PlGF production and melanoma progression has been suggested. To investigate whether PlGF might have a role in protecting melanoma cells from the cytotoxic effects of the anticancer agent temozolomide (TMZ), which is used for the treatment of this malignancy, we stably transfected a doxycycline-inducible PlGF antisense mRNA into a human melanoma cell clone that secretes VEGF-A and PlGF and expresses receptors for both growth factors. Induction of PlGF antisense mRNA in the transfected cells (13443/ASP3 subclone) halved TMZ IC50, and exogenous addition of PlGF to the culture medium 24 h before TMZ treatment, partially restored IC50 values to that of control cells. The increased sensitivity of 13443/ASP3 cells upon PlGF antisense mRNA expression was not due to down-regulation of O6-methylguanine-DNA methyltransferase, a DNA repair protein that represents the main mechanism of resistance to TMZ. Since the activity of the transcription factor nuclear factor-κB (NF-κB) has been correlated to melanoma chemoresistance, we investigated whether NF-κB was involved in PlGF-induced melanoma cell resistance to TMZ. Induction of PlGF antisense mRNA in 13443/ASP3 cells halved the levels of active NF-κB and the specific inhibition of this transcription factor increased sensitivity of 13443/ASP3 cells to TMZ. In conclusion, our data strongly suggest that PlGF plays a role in melanoma cell resistance to TMZ through a pathway that involves NF-κB activation.

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January 2011
Volume 38 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Levati, L., Ruffini, F., Muzi, A., Umezawa, K., Graziani, G., D'Atri, S., & Lacal, P.M. (2011). Placenta growth factor induces melanoma resistance to temozolomide through a mechanism that involves the activation of the transcription factor NF-κB. International Journal of Oncology, 38, 241-247. https://doi.org/10.3892/ijo_00000844
MLA
Levati, L., Ruffini, F., Muzi, A., Umezawa, K., Graziani, G., D'Atri, S., Lacal, P. M."Placenta growth factor induces melanoma resistance to temozolomide through a mechanism that involves the activation of the transcription factor NF-κB". International Journal of Oncology 38.1 (2011): 241-247.
Chicago
Levati, L., Ruffini, F., Muzi, A., Umezawa, K., Graziani, G., D'Atri, S., Lacal, P. M."Placenta growth factor induces melanoma resistance to temozolomide through a mechanism that involves the activation of the transcription factor NF-κB". International Journal of Oncology 38, no. 1 (2011): 241-247. https://doi.org/10.3892/ijo_00000844