Ovarian cancer cisplatin-resistant cell lines: multiple changes including collateral sensitivity to Taxol
Abstract
Alteration in apoptosis pathways (in particular mutations of p53 gene) may result in resistance of ovarian carcinoma to cisplatin. However, cisplatin resistance is likely to be multifactorial. An understanding of the molecular alterations associated with the development of resistance may be of considerable relevance in an attempt to optimize the therapeutic approach. Two cisplatin-resistant sublines (IGROV-1/Pt0.5 and IGROV-1/Pt1), both characterized by mutant p53 (Cancer Res 1996; 56: 556-62), but with different degree of resistance were studied in terms of pattern of cross-resistance, susceptibility to drug-induced apoptosis, expression of gluthathione-dependent system, cellular pharmacokinetics, drug-induced DNA damage. The resistance index (ratio between the IC50 of resistant and sensitive cells) after a 96-hour drug exposure was 10 for IGROV-1/Pt0.5 and 14 for IGROV-1/Pt1 cells. Resistant cells were cross-resistant to DNA-damaging agents and, interestingly, they had a collateral sensitivity to Taxol. The cellular response to Taxol paralleled the drug ability to induce apoptosis. The intracellular glutathione level was significantly increased in IGROV-1/Pt cells compared to the sensitive counterpart. In contrast, glutathion...Continue Reading
Citations
p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis