In vitro and in vivo inhibition of epidermal growth factor receptor-tyrosine kinase pathway by photodynamic therapy.

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.

• Authors: N Ahmad, K Kalka, H Mukhtar
• Journal: Oncogene (Oncogene) Vol. 20 Issue 18 Pg. 2314-7 (Apr 26 2001) ISSN: 0950-9232 [Print] England
• PMID: 11402326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Indoles
• Photosensitizing Agents
• phthalocyanine Pc 4
• ErbB Receptors

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Carcinoma, Squamous Cell (drug therapy, enzymology, pathology)
• Cell Cycle (drug effects, physiology)
• ErbB Receptors (antagonists & inhibitors, biosynthesis)
• Humans
• Immunoblotting
• Indoles (pharmacology)
• Mice
• Mice, Hairless
• Mice, Inbred SENCAR
• Photochemotherapy
• Photosensitizing Agents (pharmacology)
• Skin Neoplasms (drug therapy, enzymology, pathology)