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Combination of Phosphatidylinositol 3‐Kinases Pathway Inhibitor and Photodynamic Therapy in Endothelial and Tumor Cells
Author(s) -
Fateye Babasola,
Li Weihua,
Wang Chenguang,
Chen Bin
Publication year - 2012
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2012.01160.x
Subject(s) - verteporfin , autophagy , cancer research , photodynamic therapy , pi3k/akt/mtor pathway , programmed cell death , cancer cell , kinase , microbiology and biotechnology , phosphatidylinositol , flux (metallurgy) , cell , apoptosis , cancer , medicine , biology , signal transduction , chemistry , biochemistry , retinal , organic chemistry , choroidal neovascularization
Tumor recurrence due to incomplete eradication of tumor cells is a major problem facing current cancer therapies. To overcome this problem, it is necessary to enhance cell killing and/or prevent cell regrowth after treatment. Because phosphatidylinositol 3‐kinases (PI3K) pathway plays an important role in stimulating cell survival and growth, we studied the feasibility of using a PI3K pathway inhibitor NVP‐BEZ235 (BEZ235) to enhance the effectiveness of vascular‐targeted photodynamic therapy (vPDT) with verteporfin. We found that BEZ235 or PDT alone significantly inhibited cell growth in both SVEC endothelial and PC‐3 prostate cancer cells, although SVEC cells appeared to be more responsive than PC‐3 cells. Autophagy was detected after both BEZ235 and verteporfin‐PDT in both cell lines. Autophagy appeared to protect cells from PDT‐induced cell death because inhibition of autophagy increased cell death. Autophagic flux assay revealed that PDT actually decreased autophagic flux especially at a high dose of verteporfin. Combination of BEZ235 and PDT caused greater inhibition of PI3K signaling pathway, leading to enhanced cell growth inhibition in both cell lines. SVEC cells exhibited a higher sensitivity towards such a combination than PC‐3 cells. Our data indicated that BEZ235 in combination with PDT provides a promising approach of enhancing therapeutic response.