ErbB3 expression predicts sensitivity to elisidepsin treatment: in vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines

  • Authors:
    • Cristina Teixidó
    • Elisabet Arguelaguet
    • Berta Pons
    • Miguel Aracil
    • Jose Jimeno
    • Rosa Somoza
    • Roso Marés
    • Santiago Ramón y Cajal
    • Javier Hernández-Losa
  • View Affiliations

  • Published online on: April 3, 2012     https://doi.org/10.3892/ijo.2012.1425
  • Pages: 317-324
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Abstract

Irvalec® (elisidepsin trifluoroacetate, PM02734) is a novel marine-derived cyclic peptide belonging to the Kahaladide family of compounds, currently in clinical trials with preliminary evidence of antitumor activity. Previous studies have shown a correlation between elisidepsin sensitivity and expression of the ErbB3 receptor in a panel of NSCLC cell lines. We have studied the effect of elisidepsin on the ErbB3 pathway, characterizing the expression of all members of the ErbB (HER) family of receptors and their main downstream signaling effectors, such as Akt and MAPK. Interestingly, we observed a downregulation of ErbB3 upon elisidepsin treatment that correlates with a reduction in the Akt phosphorylation levels in the most sensitive cell lines, whereas ErbB3 levels are not affected in the less sensitive ones. Also, we observed that the basal levels of ErbB3 protein expression show a significant correlation with cell viability response against elisidepsin treatment in 14 different cell lines. Furthermore, we analyzed the combination of elisidepsin with different chemotherapeutics agents, such as cisplatin, paclitaxel and gemcitabine, in a panel of different breast (MDA-MB-435, MDA-MB-231 and MCF7), lung (HOP62, DV90 and A549) and colorectal cancer cell lines (DLD1 and HT29). IC50 values for the different drugs were tested. We observed a synergistic effect in all cell lines tested with any chemotherapeutic agent. More importantly, the two in vitro elisidepsin-resistant cell lines (MDA-MB-231 and HOP62) presented a synergistic effect in combination with cisplatin and paclitaxel, respectively. These results provide a rationale for further development of these combinations in an ongoing clinical trial.

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July 2012
Volume 41 Issue 1

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

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Spandidos Publications style
Teixidó C, Arguelaguet E, Pons B, Aracil M, Jimeno J, Somoza R, Marés R, Ramón y Cajal S and Hernández-Losa J: ErbB3 expression predicts sensitivity to elisidepsin treatment: in vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines. Int J Oncol 41: 317-324, 2012
APA
Teixidó, C., Arguelaguet, E., Pons, B., Aracil, M., Jimeno, J., Somoza, R. ... Hernández-Losa, J. (2012). ErbB3 expression predicts sensitivity to elisidepsin treatment: in vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines. International Journal of Oncology, 41, 317-324. https://doi.org/10.3892/ijo.2012.1425
MLA
Teixidó, C., Arguelaguet, E., Pons, B., Aracil, M., Jimeno, J., Somoza, R., Marés, R., Ramón y Cajal, S., Hernández-Losa, J."ErbB3 expression predicts sensitivity to elisidepsin treatment: in vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines". International Journal of Oncology 41.1 (2012): 317-324.
Chicago
Teixidó, C., Arguelaguet, E., Pons, B., Aracil, M., Jimeno, J., Somoza, R., Marés, R., Ramón y Cajal, S., Hernández-Losa, J."ErbB3 expression predicts sensitivity to elisidepsin treatment: in vitro synergism with cisplatin, paclitaxel and gemcitabine in lung, breast and colon cancer cell lines". International Journal of Oncology 41, no. 1 (2012): 317-324. https://doi.org/10.3892/ijo.2012.1425