Colorectal cancer cell lines made resistant to SN38-and Oxaliplatin: Roles of altered ion transporter function in resistance?

Christensen Sandra, Niels Frank Jensen, Johanne Danmark Stoeckel, Kirstine C. Belling, Maria Unni Romer, Ramneek Gupta, Nils Brunner, Stine Helene Falsig Pedersen, Jan Stenvang

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    Abstract

    Colorectal cancer (CRC) is the 3rd most common cancer globally, with 5year survival rates of ~50%. Response rates to standard treatments (irinotecan (SN38) or Oxaliplatin (Oxp)) are 31–56% and drug resistance is a major problem. Thus, we established in vitro CRC models to investigate SN38 and Oxp resistance in HCT-116, HT-29 and LoVo cells. Microarray analysis and qPCR validation showed that mRNA expression of glutamate transporters SLC1A1 and SLC1A3 were markedly altered in resistant cells. Remarkably, mRNA levels of SLC1A3 were increased by ~40-and ~2500-fold in SN38-and Oxp-resistant HT29 cells, respectively. Studies are ongoing to assess glutamate uptake in parental and resistant CRC cells and the effect of inhibition/knockdown of SLC1A1 and -3 on SN38- and Oxp resistance.

    In conclusion, SN38-and Oxp-resistance in CRC cells is associated with SLC1A1 and -3 dysregulation. As these transporters have not previously been implicated in SN38 or Oxp resistance and are generally restricted to the CNS, they are potential novel biomarkers for resistance and interesting candidates for therapeutic targeting.
    Original languageEnglish
    Article numberlb452
    JournalF A S E B Journal
    Volume27
    ISSN0892-6638
    Publication statusPublished - 2013
    EventJoint Annual Meeting of the ASPET/BPS at Experimental Biology - Boston, United States
    Duration: 20 Apr 201324 Apr 2013

    Conference

    ConferenceJoint Annual Meeting of the ASPET/BPS at Experimental Biology
    CountryUnited States
    CityBoston
    Period20/04/201324/04/2013

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