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Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer
- Source :
- Cellular and molecular life sciences : CMLS. 59(8)
- Publication Year :
- 2002
-
Abstract
- Stable transfection of human ovarian carcinoma cells with survivin cDNA caused a four- to sixfold increase in cell resistance to taxotere and taxol (two-sided Student's t test, p0.05), with a concomitant reduction in the apoptotic response to taxol, but did not affect cell sensitivity to cisplatin or oxaliplatin. Such findings were indirectly supported by similar observations obtained with clinical tumours. In fact, high levels of survivin protein expression (30% positive cells), detected by immunohistochemistry in 90/124 (73%) advanced ovarian carcinomas, were significantly associated with clinical resistance to a taxol/platinum-based regimen but unrelated to tumour shrinkage following cisplatin-including combinations (non-taxol based). In the 95 patients receiving a taxol/platinum-based regimen, survivin overexpression correlated with a lower clinical or pathologic complete remission rate than absent/low protein expression (43 vs 75%, p = 0.0058 by logistic regression adjusted for tumour stage, histological grade and p53 expression). Conversely, in the 29 cases treated with cisplatin-containing regimens (not taxol based), survivin expression was unrelated to tumour response. Cellular studies and clinical data suggest a direct link between survivin expression and tumour cell susceptibility to taxol.
- Subjects :
- Low protein
endocrine system diseases
Organoplatinum Compounds
Paclitaxel
Chromosomal Proteins, Non-Histone
Survivin
Cell
Apoptosis
Docetaxel
Biology
Transfection
Inhibitor of Apoptosis Proteins
Cellular and Molecular Neuroscience
Ovarian carcinoma
medicine
In Situ Nick-End Labeling
Tumor Cells, Cultured
Humans
Phosphorylation
Molecular Biology
Pharmacology
Cisplatin
Ovarian Neoplasms
Phosphotransferases
Cell Biology
medicine.disease
Molecular biology
Antineoplastic Agents, Phytogenic
Neoplasm Proteins
Oxaliplatin
medicine.anatomical_structure
Drug Resistance, Neoplasm
Mutation
Cancer research
Molecular Medicine
Immunohistochemistry
Female
Taxoids
Ovarian cancer
Microtubule-Associated Proteins
medicine.drug
Subjects
Details
- ISSN :
- 1420682X
- Volume :
- 59
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cellular and molecular life sciences : CMLS
- Accession number :
- edsair.doi.dedup.....7e3a662cf08b3fecf56d6f37b710ad5f