Abstract

Ovarian cancer is a gynecological disease and is the ninth cause of death by cancer in Chilean women. For its treatment, nucleoside-analog drugs such as gemcitabine have been extensively used, often when there is resistance to platinum-based chemotherapy. Nucleoside equilibrative (hENT) and concentrative (hCNT) transporters play a key role in the uptake and metabolism of these drugs. The expression of these transporters varies in ovarian tumor tissue compared to normal, as well as in the different histological types of ovarian cancer. We studied the differential expression of hENT1, hENT2 and hCNT1 in samples from patients diagnosed with ovarian cancer with different histotypes. Methods: Ovarian tumor samples from 10 paclitaxel/carboplatin-treated and non-treated patients, with pre-surgical diagnose of ovarian tumor, where characterized by immunohistochemistry into the different ovarian cancer histotypes. The mRNA level of hENT1, hENT2 and hCNT1 was determined in the tumor samples as well as in human ovarian cancer cell lines (SKOV-3, OVCAR-3 and OVCAR-420) by semiquantitative RT-PCR. Results: Malignant ovarian tumor tissues, as well as the cancer cell lines tested, showed higher expression of hENT1 compared with benign cyst sample (~1.4-fold) and to normal fallopian oviductal tissue (~2.7-fold). This result correlates with the resistance to treatment with paclitaxel. hCNT1 expression was downregulated in ~20% of the malignant serous histological subtypes studied. Conclusions: These results agree with previous evidences in human ovarian cancer, showing a decrease in hCNT1, and increase at hENT1 expression, mainly in the serous subtypes in comparison to non-malignant tissues. Since lower expression of NT correlates with poor prognosis ovarian cancer histotypes, the latter must be considered at the moment of defining the most appropriate treatment for each patient. Supported by CONICYT ACT-73 (PIA), FONDECYT 1080534 & 1070865 (Chile), and AECID A/024549/09 (Spain).