Anti-tumor effect of the inhibitor of cholesterol synthesis pathway – lovastatin and photodynamic therapy in colorectal cancer in vitro

• Autorzy: Osiecka B. J. , Olbromski M. , Wojdat E. , Kwiatkowski S. , Borska S.

Warianty tytułu

PL

Efekt antynowotworowy inhibitora szlaku syntezy cholesterolu – lowastatyny i terapii fotodynamicznej w raku jelita grubego in vitro

• Języki publikacji: EN

Abstrakty

EN

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.

PL

Terapia fotodynamiczna (ang. photodynamic therapy, PDT) jest obiecującą metodą w leczeniu nowotworowych i nienowotworowych schorzeń. Działanie PDT wymaga użycia fotouczulacza, światła i tlenu komórkowego, dla uzyskania wybiórczego cytotoksycznego efektu w komórkach patologicznych. Efekt ten jest wynikiem powstania wolnych rodników (ROS). Badania pokazują, że PDT z kwasem aminolewulinowym (ALA) jest skuteczna w leczeniu raka jelita grubego. Jednak efekty PDT in vivo, ze względu na niski poziom oksygenacji guza, mogą odbiegać od działania PDT in vitro. Dane eksperymentalne potwierdzają rolę cholesterolu w procesie onkogenezy i wskazują na zaburzony szlak syntezy cholesterolu, m.in. w raku jelita grubego. Statyny, np. lowastatyna, należą do inhibitorów 3-hydroksy-3-metylo-glutarylo-koenzymu A (HMG-CoA) − enzymu szlaku syntezy cholesterolu. Potencjał antynowotworowy statyn, antyproliferacyjny i proapoptotyczny, wykazano w nowotworach in vitro i in vivo. Rak jelita grubego, cechujący się mutacjami genów związanych z apoptozą, wykazuje oporność na standardowe chemioterapeutyki. Celem pracy było zbadanie efektu antyproliferacyjnego i cytotoksycznego lowastatyny i ALA-PDT (w niskiej dawce) działających osobno, oraz w metodzie połączonej (lowastatyna i PDT) – na indukcję apoptozy w przerzutowej linii raka jelita grubego SW620. Wyniki pokazały, że lowastatyna hamuje wzrost komórek w związku zależnym od dawki i czasu inkubacji. ALA-PDT w niskiej dawce działa cytotoksycznie, ale nie inicjuje apoptozy. Natomiast preinkubacja komórek raka z lowastatyną (IC50) zwiększa efekt cytotoksyczny po PDT i indukuje apoptozę w komórkach, co wykazano w teście z aneksyną V na cytometrze przepływowym. Nasze wyniki po raz pierwszy demonstrują skuteczność metody łączonej: ALA-PDT i inhibitora syntezy szlaku cholesterolu – lowastatyny, w zwiększeniu cytotoksyczności i indukcji apoptozy w komórkach raka jelita grubego, opornego na chemioterapię.

Słowa kluczowe

EN

lovastatin; aminolaevulinic acid; photodynamic therapy; apoptosis

PL

lowastatyna; kwas aminolewulinowy; terapia fotodynamiczna; apoptoza

• Wydawca: Jacek Doskocz
• Czasopismo: Acta Bio-Optica et Informatica Medica. Inżynieria Biomedyczna
• Rocznik: 2017
• Tom: Vol. 23, nr 1
• Strony: 37--48
• Opis fizyczny: Bibliogr. 31 poz.

Twórcy

autor

Osiecka B. J.

• Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu, Katedra Patomorfologii, 50-368 Wrocław, ul. Marcinkowskiego 1

autor

Olbromski M.

• Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu, Katedra i Zakład Histologii i Embriologii, 50-368 Wrocław, ul. Chałubińskiego 6A

autor

Wojdat E.

• Polska Akademia Nauk, Instytut Immunologii i Terapii Doświadczalnej im. Ludwika Hirszfelda, 53-114 Wrocław, ul. Weigla 12

autor

Kwiatkowski S.

• Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu, Katedra Patomorfologii, 50-368 Wrocław, ul. Marcinkowskiego 1

autor

Borska S.

• Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu, Katedra i Zakład Histologii i Embriologii, 50-368 Wrocław, ul. Chałubińskiego 6A

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