Medycyna fotodynamiczna / Photodynamic medicine
Anti-tumor effect of the inhibitor of cholesterol synthesis pathway – lovastatin and photodynamic therapy in colorectal cancer in vitro / Efekt antynowotworowy inhibitora szlaku syntezy cholesterolu – lowastatyny i terapii fotodynamicznej w raku jelita grubego in vitro (37-48)
Autorzy: Beata Joanna Osiecka, Mateusz Olbromski, Elżbieta Wojdat, Stanisław Kwiatkowski, Sylwia Borska
Photodynamic therapy (PDT) is a promising treatment method for non-oncological and oncological diseases. PDT requires the use of photosensitizer, light, and cell oxygen. A selective, cytotoxic effects can be achieved in cancer cells, thanks to formation of radical oxygen species (ROS). Recent data indicate, that PDT with aminolevulinic acid (ALA) is successful in treatment of colorectal cancer. However, anti-cancer effects PDT in vivo, can vary in PDT in vitro, due to low level of oxygenation of tumor cells. Experimental research confirms the role of cholesterol in oncogenesis and indicates, that in colorectal cancer the cholesterol synthesis is disrupted; among others lovastatin belong to inhibitors 3-hydroxy-3-methyl-glutharyl-coenzyme A (HMG-CoA) enzyme of cholesterol synthesis pathway. Anti-tumor potential of statins: antiproliferative and pro-apoptotic, were demonstrated in various tumors in vitro and in vivo. Colorectal cancer, which often has genes mutations that are related to programmed death cells, shows resistance to chemotherapy. The objective of the research was to investigate the effect of antiproliferative and cytotoxic lovastatin and ALA-PDT (in low dose) working separately and in combination method (lovastatin and PDT) − for apoptosis induction, in metastatic colon cell line SW620. Our finding showed, that lovastatin inhibits the growth of cancer cells, depending on the dose and incubation time. ALA-PDT in low dose works on cell cytotoxic, yet do not initiate apoptosis. Whereas, preincubation of cells with lovastatin (IC50) increases the cytotoxic effect after PDT and induces apoptosis in cancer cells SW620, as demonstrated using an assay of Annexin V for flow cytometry. Our research demonstrates for the first time, the effectiveness of ALA-PDT connection with an inhibitor of cholesterol synthesis pathway – lovastatin, in increasing the cytotoxicity and induction of apoptosis in colon cancer cells, that are resistant to chemotherapy.
Keywords: lovastatin, aminolaevulinic acid, photodynamic therapy, apoptosis