Insulin-Like Growth Factor-2 Is Induced Following 5-Aminolevulinic Acid-Mediated Photodynamic Therapy in SW620 Human Colon Cancer Cell Line.

Marta Woźniak,Kamila Duś-Szachniewicz,Piotr Ziółkowski

doi:10.3390/ijms161023615

Marta Woźniak, Kamila Duś-Szachniewicz + Show 1 more

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https://doi.org/10.3390/ijms161023615

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Abstract

The IGF system is a family of polypeptide growth factors, which plays a significant role in the development and growth of many cells. Dysregulation of insulin-like growth factors and their pathway components has been connected with essential tumor properties, such as tumor cell proliferation, antiapoptotic properties, invasive behavior and chemotherapy resistance. However, the effects of photodynamic therapy (PDT), one of the cancer treatment methods for the regulation of the IGF signaling pathway, are still unclear. The aim of this study was to investigate the expression of IGF-2 after 5-aminolevulinic acid (5-ALA)-mediated-PDT in SW620 human colorectal cancer cells with evaluation of cell proliferation and apoptosis and to determine the effects of PDT on the IGF-2 receptor (IGF-2R), IGF-2 binding protein-1 (IGF-2BP-1) and the proapoptotic protein, BAX. Cells were treated with 5-aminolevulinic acid and its methyl ester. Changes of the expression and concentration of IGF-2 before and after treatment were assayed by immunocytochemistry, Western blot and ELISA. We found that IGF-2 was significantly overexpressed in the SW620 cell line, while its receptor and binding protein-1 were not significantly changed. Within this study, we would like to suggest that IGF-2 contributes to the effects of PDT and that its expression will influence post-PDT efficacy.

Highlights

Colorectal cancer is the third most frequently-diagnosed malignant tumor worldwide (1.23 million, 9.7% after lung and breast cancer), and its incidence has been increasing in recent years [1]
To identify the best concentration of photosensitizer precursor for low dose photodynamic therapy, various levels of 5-aminolevulinic acid (5-ALA) and met-ALA were cultured within cancer cells in the preliminary study
Cells incubated with 5-ALA only showed a slight significant increase of cell proliferation (p = 0.043), while cells treated with met-ALA insignificantly reduced their viability; whereas the cell survival rate after irradiation with 4.5 J/cm2 decreased significantly (p < 0.05) up to 67% for 5-ALA and 59% for met-ALA (Figure 1)

Summary

Introduction

Colorectal cancer is the third most frequently-diagnosed malignant tumor worldwide (1.23 million, 9.7% after lung and breast cancer), and its incidence has been increasing in recent years [1]. What is important is that an expected decrease in the risk of colon cancer is associated with improved treatment, increased awareness and its early detection. Conventional chemotherapeutic agents, often effective, are highly toxic because of their lack of selectivity for cancer cells. The photodynamic method known as photodynamic therapy (PDT) is widely used as a diagnostic method and mode of treatment without the above-mentioned drawback. It comprises three agents: a light-sensitive drug, visible light at the appropriate wavelength, reactive oxygen species or singlet oxygen. Following low-dose light irradiation (4.5 J/cm mW/cm2), the expression of insulin-like growth factor-2 (IGF-2) system components was evaluated in the SW620 colon cancer cell line

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