Abstract
Multi-drug resistance (MDR) is the main cause of low effectiveness of cancer chemotherapy. P-glycoprotein (P-gp) is one of the main factors determining MDR. Some studies indicate the potential role of melatonin (MLT) in MDR. In this study, we examined the effect of MLT on colon cancer cell’s resistance to doxorubicin (DOX). Using the sulforhodamine B (SRB), method the effect of tested substances on the survival of LoVo (colon cancer cells sensitive to DOX) and LoVoDX (colon cancer cells resistant to DOX) was rated. Using immunocytochemistry (ICC), the expression of P-gp in the LoVo and LoVoDX was determined. With the real-time PCR (RT-PCR) technique, the ABCB1 expression in LoVoDX was evaluated. Based on the results, it was found that MLT in some concentrations intensified the cytotoxicity effect of DOX in the LoVoDX cells. In the ICC studies, it was demonstrated that certain concentrations of MLT and DOX cause an increase in the percentage of cells expressing P-gp, which correlates positively with ABCB1 expression (RT-PCR). The mechanism of overcoming resistance by MLT is probably not only associated with the expression of P-gp. It seems appropriate to carry out further research on the use of MLT as the substance supporting cancer chemotherapy.
Highlights
Over many years of in vivo and in vitro research, differences in the sensitivity of certain cancer cells to chemotherapy have been observed
Using real-time PCR, we showed that MLT alone does not significantly affect the expression of the At(wpaCehFxtoBohiepttgmCheeruArBneebUersBt1iceaissnCoasgiiiont6n,BneenAgcan1gdete)orMngt.etfihhtenaCLPrenelaTL--oegttgcmoiiewpoomiVnnnbnioceeticohLDoneePmfXoixnDnCVKptpcgOrRero1aaelX,DrtMl(sewiXs0soa.d.Licen9tDoeTtansμolOolhllMsfwocXo.tfeKew)iDlPat,sl1httseD-Oegda(tdOD0Xprcet.XcO9hocaaoonatXtμsnemtciMdacgeMaepnnoctn)atLi,onrfitraTraDnlecalytcdlaOiateoniwlttonXonetoniltnstyrocsstheaeefiitgtdnltdoKilhnocso2teirncehtfeor(iscea0ceonyasn.aLf0ctentoooe9KedttsnVdlμ2tysAtoaMrioDtg(Baini0nXnt)cC.lic0isyo(Bcfri9Fnieeg1wcilasngμalgisinutcMteefihuotrndcle)ltyeathtAu6snheaeiBrtBexgflec)fypCn.eypLriBcdtfeoooti1estcVstcesahtgrionanoeeeDtttanniiXelacsyextec((epdFFeeddrxii,legglepwtcsuuhcrrshrereeuieeeoaslgrstsn66eueieBAonaord)nsee)f,
Many in vitro studies have demonstrated the anti-proliferative activity of MLT on tumor cells, including breast cancer—MCF-7, melanoma and colon adenocarcinoma—LoVo [41,42,43,44,45]
Summary
Over many years of in vivo and in vitro research, differences in the sensitivity of certain cancer cells to chemotherapy have been observed. This phenomenon is one of the biggest problems of contemporary oncology, and is defined as multidrug resistance (MDR). The classical MDR mechanism is conditioned by the membrane transport proteins Their task is to remove the chemotherapeutic agent from the cell, which reduces its effectiveness by decreasing the intracellular concentration [3]. These proteins belong to the group of ABC (ATP-Binding Cassette) transporters [4]. The best known protein from this group is P-glycoprotein (P-gp) [5]
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