| Abstract | Rak debelog crijeva (CRC) je jedan od vodećih uzroka smrti uzrokovanih
karcinomom u svijetu. Incidencija ovisi o geografskom položaju, načinu
života i genetskim faktorima. CRC se očituje stvaranjem adenomatoznih
polipa na unutarnjem zidu debelog crijeva. Liječenje CRC-a se odvija putem
operativnih zahvata, radijacije, kemoterapije ili kombinacije više opcija. 5-
FU je jedan od vodećih kemoterapeutskih opcija za liječenje CRC-a, ali zbog
česte pojave kemorezistencije tumorskih stanica, potrebno je razmatrati
nove opcije liječenja. Fitokemikalije pokazuju obećavajući potencijal
zahvaljujući svojem širokom spektru pozitivnih učinaka, među kojima je i
protutumorsko djelovanje. Cilj ovog rada je bio istražiti protutumorsko
djelovanje fitokemikalija rutina i kvercetina, te njihov učinak u kombinaciji
s 5-FU na tumorske stanice debelog crijeva HCT116. Korišteni su 24-satni
tretmani rutina, kvercetina, 5-FU i njihovih kombinacija, čije je djelovanje
ispitano korištenjem XTT-a, Western blota i imunofluorescencije. Rezultati
su pokazali citotoksičan učinak rutina i kvercetina koji je pojačan u
kombinaciji s 5-FU, aktivaciju autofagije te intrinzičnog i ekstrinzičnog puta
apoptoze, s pojačanim aktivacijama u kotretmanima s 5-FU, te utjecaj na
ERK/MAPK signalnu kaskadu i FoxO3a transkripcijski faktor. Pokazalo se da
su kombinacijske terapije učinkovitije od zasebnih, te da je rutin u
kombinaciji s 5-FU najučinkovitija kombinacija. Rutin, iako skromnijeg
djelovanja u zasebnom tretmanu, djeluje kao kemosenzitizator 5-FU-a,
pojačavajući njegov utjecaj na tumorske stanice. Ipak, potrebno je
provođenje istraživanja in vivo kako bi se pobliže ustanovilo djelovanje
fitokemikalija zasebno i u kombinaciji s kemoterapeuticima unutar
organizma. |
| Abstract (english) | Colorectal cancer (CRC) is one of the leading causes of cancer-related death
worldwide. The incidence depends on geographical location, lifestyle, and
genetic factors. CRC is manifested through the formation of adenomatous
polyps on the inner wall of the colon. CRC is treated with surgery, radiation,
chemotherapy, or a combination of several options. 5-FU is one of the
leading chemotherapeutic options for the treatment of CRC, but due to the
frequent appearance of drug resistance in tumor cells, it is necessary to
consider new treatment options. Phytochemicals show promising potential
thanks to their wide spectrum of positive effects, among which is antitumor
activity. The aim of this work was to investigate the antitumor activity of
the phytochemicals rutin and quercetin, and their effect in combination with
5-FU in HCT116 colon tumor cells. 24-hour treatments of rutin, quercetin,
5-FU and their combinations were used, the effects of which were tested
using XTT, Western blot and immunofluorescence. The results showed the
cytotoxic effect of rutin and quercetin, which was enhanced in combination
with 5-FU, the activation of autophagy and the intrinsic and extrinsic
pathway of apoptosis, with increased activation in co-treatments with 5-FU,
and the impact on the ERK/MAPK signaling cascade and the FoxO3a
transcription factor. It has been shown that combination therapies are more
effective than separate therapies, and that rutin combined with 5-FU is the
most effective combination. Rutin, although of a more modest effect in a
separate treatment, acts as a chemosensitizer of 5-FU, enhancing its effect
on tumor cells. However, it is necessary to carry out research in vivo to
establish the action of phytochemicals separately and in combination with
chemotherapeutics inside the organism in a more detailed manner. |
