The iron chelator desferrioxamine synergizes with chemotherapy for cancer treatment.

Abstract

BACKGROUND:

Cisplatin (CDDP) resistance remains a major obstacle for treatment of ovarian cancer. Iron contributes to the growth and reproduction of malignant cells, thus iron chalators can inhibit the growth of tumor cells by depleting the intracellular iron pool. The iron chelator, desferrioxamine (DFO), has performed anticancer in previous study. The aim of our study is to determine the correlation between iron-deprivation and tumor chemosensitivity in ovarian cancer.

METHODS:

To investigate the prognostic value of ferritin light (FTL), ferroportin (FPN), hepcidin (HAMP) and divalent metal-ion transporter-1 (DMT1) in ovarian cancer, the Kaplan-Meier analysis and the Gene Expression Profiling Interactive Analysis (GEPIA) were used. The ovarian cancer cell lines (SKOV-3 and OVCAR-3) were exposed to a gradient concentration of DFO (10, 20, 50, 100, 200 μM) and CDDP (1, 5, 10, 50,100 μM) for 24 h. The protein expression of FTL was tested. The expression of cancer stem cell (CSC) markers, including Sox2, Nanog and C-myc, were downregulated with treatment of DFO. Also, the mamosphere formation and the plation of CD44+/high/CD133+/high and Aldehyde dehydrogenase (ALDH)+/high SKOV-3 cells were reduced after treatment for 7d. Furthermore, we detected the expression of p53, BCL-2, BAX, and caspase-8.

RESULTS:

The survival analysis revealed that high expression of FTL, DMT1, HAMP, showed poor overall survival (OS) in ovarian cancer patients. Our combined data found that DFO could effectively inhibit CSCs, improve the resistance to chemotherapy, and significantly enhanced the efficacy of CDDP therapy in vitro in promoting apoptosis. Besides, targeting molecular targets, including BAX, BCL-2, p53 and caspase-8 could serve as the clinical biomarkers to evaluate the effects of ovarian cancer. It is reasonable to believe that DFO adjuvant therapy in combination with CDDP chemotherapy can promote the improvement of treatment response in ovarian cancer patients.

CONCLUSION:

Our research suggests the experimental evidence for DFO and CDDP as a new effective combination therapy to enhance the efficacy of chemical therapy in ovarian cancer.

• Authors: Lingjuan Wang, Xiaoqing Li, Yanxi Mu, Chang Lu, Shiqian Tang, Kun Lu, Xiaoming Qiu, Aili Wei, Yongjiu Cheng, Wei Wei
• Journal: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (J Trace Elem Med Biol) Vol. 56 Pg. 131-138 (Dec 2019) ISSN: 1878-3252 [Electronic] Germany
• PMID: 31466045 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier GmbH. All rights reserved.

Chemical References

• Antigens, CD
• Antineoplastic Agents
• Iron Chelating Agents
• Tumor Suppressor Protein p53
• Iron
• Aldehyde Dehydrogenase
• Deferoxamine
• Cisplatin

Topics

• Aldehyde Dehydrogenase (metabolism)
• Antigens, CD (metabolism)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology, therapeutic use)
• Deferoxamine (pharmacology, therapeutic use)
• Disease Progression
• Drug Synergism
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Intracellular Space (metabolism)
• Iron (metabolism)
• Iron Chelating Agents (pharmacology, therapeutic use)
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Tumor Suppressor Protein p53 (metabolism)