Microarray-based detection and expression analysis of ABC and SLC transporters in drug-resistant ovarian cancer cell lines

Discovery of microarray-identified genes associated with ovarian cancer progression

“…6), in which these four genes were found to directly/indirectly interact with 15 TSGs and 25 oncogenes that all play important roles in the regulation of drug resistance in ovarian cancer (27,28). Consistent with our conclusions, the previous studies indicated that ADH1B and ABCA8 may be associated with drug resistance in ovarian cancer (45,46). ADH1B encodes a critical enzyme in alcohol metabolism, and may cause variations in the amount of production and/or oxidation of acetaldehyde between individuals (47).…”

“…5). However, a controversial study indicated that ABCA8 was significantly downregulated in methotrexate, cisplatin, doxorubicin, vincristine, topotecan and paclitaxel-resistant variant of the w1 ovarian cancer cell line (46). Associations of ALDH1A2 with ovarian cancer is rare, with only one study indicating that ALDH1A2 is a widespread stem-cell marker expressed in both ovarian surface epithelium and epithelium of oviductal fimbriae in which high-grade serous ovarian carcinomas may originate (56).…”

New and Old Genes Associated with Topotecan Resistance Development in Ovarian Cancer Cell Lines

“…Expression of BCRP has been reported by others in ovarian cancer cell lines exposed to TOP (13,17) as well as in many drug-resistant solid tumors and was associated with mitoxantrone, topotecan, irinotecan, flavopiridol and methotrexate resistance (14,17). Previously we also observed an increased expression of ABCG2 gene in TOP-resistant variants of A2780 (15,16) and W1 cell lines (18,39). These results indicate that increased expression of BCRP transporter is the main mechanism of TOP resistance in ovarian cancer.…”

Drug metabolism and clearance system in tumor cells of patients with multiple myeloma

“…However, a clinical trial with a potent and specific inhibitor to ABCB1 (Zosuquidar) did not show any benefit in progression free or overall survival suggesting additional transporters or mechanisms are involved in conferring drug resistance [39]. Our data suggest that several ABC transporters are involved in the primary drug resistance phenotype, which could justify at least in part the limited therapeutic success of monotargeted therapies and imply, in accordance with previous studies, that ABC transporter family could exhibit a high degree of functional redundancy [40,41]. Moreover, our data strongly suggest that in cancer drug resistant or sensitive phenotype, more concern should be given to the ratio of efflux (ABC transporters) versus influx transporters (SLC transporters) rather than considering efflux proteins solely.…”