Abstract
Background . Chemotherapy is one of the main types of treatment in ovarian cancer. Standard first-line treatment includes platinum drugs. Every fifth patient develops chemoresistance after platinum-containing first line therapy. Glutathione detoxification systems play an important role in platinum drugs utilization. Purpose. To assess the redox status of blood plasma and ascitic fluid in ovarian cancer patients before and after neoadjuvant platinum-containing chemotherapy (NACT). Materials and methods . We determined the activity of the glutathione system and thioredoxin levels in blood plasma before and after NACT and in the ascitic fluid before NACT, and the presence of GSTP1 gene polymorphism (Ile105Val (rs1695), Ala114Val (rs1138272) in 30 III–IV FIGO stage ovarian cancer patients. Patients were divided into 3 groups: NR – no relapse in 2 years after last chemotherapy course; R1 – relapse in less than 6 months; R2 – relapse in more than 6 months. Results. We established an increase of the glutathione-transferase activity and a decrease of the GSH level in plasma after chemotherapy in R1 patients, and an opposite dynamic of glutathione-transferase and GSH in the R2 group. Thioredoxin level in plasma of all patients was lower than in the control group; differences in levels between groups were not statistically significant. GSTP1 105Val allele was more frequently present in patients than in the control group, and more frequently in R2 than in R1. Conclusion . The increase in plasma glutathione-transferase and glutathione-reductase levels can be a prognostic marker of early relapse. Thioredoxine dynamics do not correlate with the chemotherapy response. The presence of the GSTP1 105Val allele is a risk factor for ovarian cancer development, but a protective factor against early relapse.
Highlights
Chemotherapy is one of the main types of treatment in ovarian cancer
Glutathione detoxification systems play an important role in platinum drugs utilization
We determined the activity of the glutathione system and thioredoxin levels in blood plasma before and after neoadjuvant platinum-containing chemotherapy (NACT) and in the ascitic fluid before NACT, and the presence of GSTP1 gene polymorphism
Summary
Оценить окислительно-восстановительный статус плазмы крови и асцитической жидкости у больных РЯ до и после неоадъювантной платиносодержащей химиотерапии (НАХТ). Мы определили активность глутатионовой системы и уровень тиоредоксина в плазме крови до и после НАХТ и в асцитической жидкости до НАХТ у 30 пациентов на III–IV стадиях (по FIGO) рака яичников. Установлено увеличение активности GT и снижение уровня GSH в плазме после химиотерапии у пациентов с Р1, а также противоположная динамика GT и GSH в группе Р2. Уровень тиоредоксина в плазме у всех пациентов был ниже, чем в контрольной группе; различия в уровнях между группами не были статистически значимыми. Присутствие аллеля 105Val в гене GSTP1 является фактором риска развития рака яичников, но защитным фактором против раннего рецидива. Ключевые слова: рак яичников, асцитическая жидкость, химиорезистентность, глутатионовая система, полиморфизм гена GSTP1. Долгова Д.Р., Генинг Т.П., Абакумова Т.В. и др
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