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Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells
- Source :
- Acta oncologica (Stockholm, Sweden). 58(11)
- Publication Year :
- 2019
-
Abstract
- Background: Arsenic compounds (As2O3 and As4O6) have demonstrated anticancer effects in various malignancies. In this study, the cytotoxicity of arsenic compounds on ovarian cancer cell lines and the anticancer activity of the combination of arsenic compounds and cisplatin IN chemoresistant ovarian cancer cells were investigated. Methods: We investigated the cytotoxicity of As2O3 and As4O6 and their combinations with cisplatin in the paclitaxel-sensitive ovarian cancer cell lines SKOV3ip1 and HeyA8 and paclitaxel-resistant ovarian cancer cell lines SKOV3TRip2 and HeyA8-MDR. Growth and apoptosis were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. For detection of apoptotic cells, immunofluorescence was performed using a cleaved caspase-3 antibody. Cell-cycle distribution was determined by propidium iodide staining and flow cytometry. Results: Treatment of each cell line with As2O3 or As4O6 led to a marked dose-dependent inhibition of cell growth. As2O3 and As4O6 treatment induced caspase-3-dependent apoptosis in all cell lines compared to the respective control groups (p 2O3 and As4O6 induced apoptosis of paclitaxel-sensitive and -resistant cancer cell lines following G2/M cell cycle arrest (p 2O3 or As4O6 in the paclitaxel-resistant ovarian cancer cell lines. Conclusions: As2O3 and As4O6 can inhibit cell growth and induce apoptosis in paclitaxel-sensitive and -resistant ovarian cancer cell lines. Their combination with cisplatin resulted in a synergistic effect in paclitaxel-resistant cancer cell lines. These results suggest that arsenic compounds may be given in monotherapy or combination therapy with cisplatin for treating paclitaxel-resistant ovarian cancer.
- Subjects :
- Paclitaxel
Antineoplastic Agents
Apoptosis
Adenocarcinoma
030218 nuclear medicine & medical imaging
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Arsenic Trioxide
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Radiology, Nuclear Medicine and imaging
MTT assay
Propidium iodide
Arsenic trioxide
Cytotoxicity
Cell Proliferation
Cisplatin
Ovarian Neoplasms
Cell growth
business.industry
Cell Cycle
Drug Synergism
Hematology
General Medicine
medicine.disease
Flow Cytometry
Oncology
chemistry
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
Female
Ovarian cancer
business
medicine.drug
Subjects
Details
- ISSN :
- 1651226X
- Volume :
- 58
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Acta oncologica (Stockholm, Sweden)
- Accession number :
- edsair.doi.dedup.....4e8a6e03dd2d8281248d2dd6da265a63