Abstract
PDT, a new therapeutic procedure for the management of many malignant conditions including skin cancer, involves the administration of a photosensitizing compound followed by illumination of the lesion with visible light. We earlier showed an involvement of: (i) WAF1/p21-cyclins (D1 and E)-cdk (2 and 6) network; and (ii) Rb/E2F-DP machinery during silicon phthalocyanine (Pc4)-PDT-mediated cell cycle dysregulation and apoptosis of human epidermoid carcinoma (A431) cells. Here, we investigated the involvement of EGFR-pathway during antiproliferative responses of Pc4-PDT in A431 cells and during ablation of murine skin papillomas. Pc4-PDT of A431 cells was found to result in a time-dependent down-modulation of the protein expression and phosphorylation of EGFR and Shc (an immediate downstream molecule in EGFR-pathway), during progressive increase in apoptotic response. To establish the relevance of these in vitro findings to in vivo situations, we subjected chemically- as well as ultraviolet B radiation-induced squamous papillomas in SENCAR and SKH-1 hairless mice, respectively, to Pc4-PDT, and assessed its effect on EGFR-pathway during ablation of these tumors. Pc4-PDT was found to result in a time-dependent: (i) inhibition of protein expressions of EGFR; and (ii) tyrosine phosphorylation of EGFR and Shc; and (iii) induction of apoptosis, during the regression of these tumors. These data suggest the involvement of EGFR-pathway during the antiproliferative effects of PDT. It is tempting to speculate that inhibitors of EGFR could enhance the therapeutic efficacy of PDT.
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Acknowledgements
This study was supported by USPHS grants RO1 CA 51802, PO1 CA 48735, P30 CA 43703 and P30 AR 39750. Nihal Ahmad is a recipient of a Career Development Award from the Dermatology Foundation, USA.
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Ahmad, N., Kalka, K. & Mukhtar, H. In vitro and in vivo inhibition of epidermal growth factor receptor-tyrosine kinase pathway by photodynamic therapy. Oncogene 20, 2314–2317 (2001). https://doi.org/10.1038/sj.onc.1204313
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DOI: https://doi.org/10.1038/sj.onc.1204313
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