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Platinum-based chemotherapy and bevacizumab instigate the destruction of human ovarian cancers via different signaling pathways.
Kingnate, Chalita; Charoenkwan, Kittipat; Kumfu, Sirinart; Apaijai, Nattayaporn; Jaiwongkam, Thidarat; Khunamornpong, Surapan; Chattipakorn, Nipon; Chattipakorn, Siriporn C.
Afiliação
  • Kingnate C; Department of Obstetrics and Gynecology, Lamphun Hospital, Lamphun 51000, Thailand; Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang
  • Charoenkwan K; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
  • Kumfu S; Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand; Cardiac Electrophysiology Unit, Departm
  • Apaijai N; Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
  • Jaiwongkam T; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
  • Khunamornpong S; Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
  • Chattipakorn N; Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand; Cardiac Electrophysiology Unit, Departm
  • Chattipakorn SC; Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Oral Biology and Diagnost
Biochem Pharmacol ; 188: 114587, 2021 06.
Article em En | MEDLINE | ID: mdl-33932471
The standard chemotherapy regimens of ovarian cancer are platinum-based chemotherapy (carboplatin and paclitaxel) and bevacizumab (BEV). However, the effects of BEV alone or combined with carboplatin and paclitaxel on mitochondrial dynamics, mitochondrial function, mitophagy, apoptosis, inflammation and vascular endothelial growth factor (VEGF) in human ovarian cancer mitochondria and cells have not yet been investigated. Therefore, we aimed to test the hypothesis that 1) platinum-based chemotherapy and BEV equally damage isolated mitochondria from human ovarian cancers, and ovarian cancer cells through inducing mitochondrial dynamics dysregulation, mitochondrial dysfunction, increased mitophagy and apoptosis, as well as altered inflammation and VEGF; and 2) combined therapies exert greater damage than monotherapy. Each isolated human ovarian cancer mitochondria (n = 16) or CaOV3 cells (n = 6) were treated with either platinum-based chemotherapy (carboplatin 10 µM and paclitaxel 5 µM), BEV (2 mg/mL) or combined platinum-based chemotherapy and BEV for 60 min or 24 h, respectively. Following the treatment, mitochondrial dynamics, mitochondrial function, mitophagy, apoptosis, cytotoxicity, inflammation and VEGF were determined. Platinum-based chemotherapy caused ovarian cancer mitochondria and cell damage through mitochondrial dysfunction, increased cell death with impairment of membrane integrity, and enhanced VEGF reduction, while BEV did not. BEV caused deterioration of ovarian cancer mitochondria and cells through mitochondrial-dependent apoptosis, but it had no effect on cell viability. Interestingly, combined platinum-based chemotherapy and BEV treatments had no addictive effects on all parameters except mitochondrial maximal respiration, when compared to monotherapy. Collectively, these findings suggest that platinum-based chemotherapy and BEV caused human ovarian cancer mitochondrial and cell damage through different mechanisms.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Protocolos de Quimioterapia Combinada Antineoplásica / Carboplatina / Paclitaxel / Bevacizumab Limite: Female / Humans / Middle aged Idioma: En Revista: Biochem Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Protocolos de Quimioterapia Combinada Antineoplásica / Carboplatina / Paclitaxel / Bevacizumab Limite: Female / Humans / Middle aged Idioma: En Revista: Biochem Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de publicação: Reino Unido