Karaciğer, prostat ve kolon kanseri hücrelerinde cisplatin ve 5FU uygulamasına çoklu ilaç direnci gen ifadesi yanıtı

Öz

Tümör hücrelerinin plazma membranında ilaç taşıyıcıların değişken ekspresyonu, ilaç direncine katkıda bulunmuştur. Bu çalışmanın amacı Hep3B, PC3 ve HT29 hücre hatlarında Cisplatin ve 5-florourasil (5FU) uygulamasının MRP2 ve MRP3 genlerinin ekspresyon seviyelerine etkilerini araştırmaktır. Cisplatin ve 5FU'nun sitotoksik etkilerini belirlemek için MTT metodu kullanıldı. MTT testinden elde edilen sonuçlar PC3 hücre hattının, 48 saat cisplatin uygulamasına en duyarlı hücre hattı olduğunu göstermiştir ve bu zaman aralığı için en düşük IC50 değerini (0.5 µg / ml) göstermiştir. 5FU uygulaması PC3 hücrelerinin çoğalmasını farklı şekillerde değiştirmiştir, 48 saat için 6.0 µg / ml ve 72 saat için8.2 µg / ml IC50 değerleri elde edilmiştir. MRP2 ve MRP3'ün mRNA ekspresyon seviyeleri, kantitatif ters transkripsiyon polimeraz zincir reaksiyonu ile belirlendi. qRT-PCR sonuçları, MRP3 mRNA ekspresyon seviyesinin cisplatin ve 5FU ile muamele edilmiş tüm hücre hatlarında genel olarak azalmaya neden olmasına ragmen, MRP2'nin PC3 ve Hep3B hücrelerinde genel olarak artışa neden olduğu belirlenmiştir.

Anahtar Kelimeler

• sitotoksisite,cisplatin,5FU,çoklu ilaç direnci

Multidrug resistance gene expression response to cisplatin and 5FU treatment in hepatoma, prostate and colon cancer cells

Öz

Variable expression of drug transporters at the plasma membrane of tumor cells contributed to drug resistance. The aim of the present study was to explore the expression levels of MRP2 and MRP3genes in Cisplatin and 5 fluorouracil (5FU) treated Hep3B, PC3 and HT29 cell lines. MTT assay was used to determine the cytotoxic effects of cisplatin and 5FU. The results from the MTT assay revealed that PC3 cell line is the most sensitive for cisplatin treatment presenting the lowest IC50 value (0.5 µg/ml) for 48h. 5FU treatment altered the proliferation of PC3 cells with the IC50 values 6.0 µg/ml for 48 h and 8.2 µg/ml for 72h. The mRNA expression levels of MRP2 and MRP3 were determined by quantitative reverse transcription polymerase chain reaction. qRT-PCR results revealed that while the expression levels of MRP3 mRNA was generally down regulated in all cell lines treated with cisplatin and 5FU, MRP2 was upregulated in PC3 and Hep3B cells.

Anahtar Kelimeler

• cytotoxicity,cisplatin,5FU,multidrug resistance

Kaynakça

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