PROFIL MicroRNA 451 (miR451) DAN P-GLYCOPROTEIN (PGP) PADA CELL LINE MCF-7 RESISTEN DOXORUBICIN (MCF-7/DOX)

Cancer is a deadly disease with high mortality and incidency. Doxorubicin (DOX) is anthracycline antitumor-antibiotic which used as chemotheurapeutic therapy against cancer. Some type of cancer cell was known to having low sensitivity or even resistant to various chemotherapy. In the previous study,...

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Bibliographic Details
Main Authors: , Fuad Gandhi Torizal, , Prof. dr. Sofia Mubarika, M.Med.Sc., Ph.D.
Format: Thesis
Published: [Yogyakarta] : Universitas Gadjah Mada 2013
Subjects:
ETD
Description
Summary:Cancer is a deadly disease with high mortality and incidency. Doxorubicin (DOX) is anthracycline antitumor-antibiotic which used as chemotheurapeutic therapy against cancer. Some type of cancer cell was known to having low sensitivity or even resistant to various chemotherapy. In the previous study, microRNA451 (miR451) estimated play a role in inhibiting mechanism by post transcription regulation of P-glycoprotein-encoding gene as transport protein in chemotherapeutic resistance mechanism. The purpose of this study is to analyze miR451 and PGP expression profile on doxorubicin-resistant MCF-7 cell line (MCF-7/DOX) and to analyze relationship between miR451 expression level and PGP expression to obtain scientific information as a reference in development of microRNA research. This study was conducted in silico to analyze miR451 and MDR1 mRNA sequence interaction. Afterwards, the laboratory-experimental study was conducted in vitro to analyze miR451 expression in doxorubicin-resistant MCF-7 cell line (MCF-7/DOX). The methods that used in this study is the periodic doxorubicin treatment in parental MCF-7 cell line to obtain resistant-MCF-7 cell line. The resistance parameter that used in this study is IC 50 value in doxorubicin-treated MCF-7 is higher than parental MCF-7 in MTT assay. PGP expression was analyzed by immunocytochemistry and miR451 expression was analyzed by qRT PCR using U6 SnRNA as reference gene and UniSp6 as positive control. The result show that no miR451 amplification were detected in both parental MCF-7 and MCF-7/DOX in qRT PCR analysis, but based on immunocytochemistry assay, PGP expression was found on MCF-7/DOX cytoplasmic and cytoplasmic membrane. Based on this in vitro study, it can be concluded that there were PGP expression in MCF-7/DOX, but there were no miR451 expression in both MCF-7 and MCF-7/DOX. By resistance induction with doxorubicin treatment, the upregulation of PGP was occurred without influence of lost expression of miR451 in MCF-7/DOX.