Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Bilimleri Enstitüsü, Fen Bilimleri Enstitüsü, Türkiye

Tezin Onay Tarihi: 2012

Öğrenci: ÇAĞRI URFALI

Danışman: UFUK GÜNDÜZ

Özet:

Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, therefore, decreased levels of intracellular drug accumulation. Despite the fact that several chemical modulators claim to restore BCRP-mediated increased drug efflux, these modulators were shown to display various side effects, precluding their clinical use. Therefore, to reverse BCRPmediated MDR phenotype by a modulator with minimum cytotoxicity may increase clinical benefits and minimize side effects.