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Combination treatment with dendrosomal nanocurcumin and doxorubicin improves anticancer effects on breast cancer cells through modulating CXCR4/NF-κB/Smo regulatory network.
- Source :
-
Molecular biology reports [Mol Biol Rep] 2017 Aug; Vol. 44 (4), pp. 341-351. Date of Electronic Publication: 2017 Jul 27. - Publication Year :
- 2017
-
Abstract
- Despite advantageous antitumor properties of doxorubicin, the considerable cytotoxicity of this chemotherapeutic agent has made it necessary to develop combination treatment strategies. The aim of the current study was to investigate the possible synergism between dendrosomal nanocurcumin (DNC) and doxorubicin in eliciting anticancer effects on MDA-MB-231 metastatic breast cancer cells. The expression levels of CXCL12/CXCR4 axis and Hedgehog pathway genes were evaluated in patient-derived breast carcinoma tissues by qRT-PCR. MTT assay, Annexin V-FITC staining followed by flowcytomety and wound healing assay were used to measure the effects caused by DNC and doxorubicin, alone and in combination, on the viability, apoptosis induction, and migration of MDA-MB-231 cells, respectively. Also, qRT-PCR was exploited to analyze the expression of Smo, NF-κB and CXCR4 in cancer cells. Our results revealed that combination treatment with DNC and doxorubicin leads to significantly decreased viability, increased apoptosis, and reduced migration of breast cancer cells compared with using each drug alone. Also, combination treatment is more efficient that single treatment in reducing the expression levels of NF-κB and Smo transcripts. Our findings provide convincing support for the notion that DNC could synergistically enhance the anticancer effects of doxorubicin on metastatic breast cancer cells by improving its anti-proliferative, pro-apoptotic, and anti-migratory activities. This may be mediated, in part, by downregulating CXCR4, NF-κB, and Smo genes. Overall, the findings of the current study suggest that DNC might be used as a synergistic agent for enhancing therapeutic efficiency and reducing toxic effects of doxorubicin on breast cancer cells.
- Subjects :
- Adult
Antineoplastic Agents pharmacology
Apoptosis drug effects
Breast Neoplasms genetics
Breast Neoplasms metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Chemokine CXCL12 metabolism
Curcumin metabolism
Doxorubicin metabolism
Drug Synergism
Female
Gene Expression Regulation, Neoplastic drug effects
Hedgehog Proteins metabolism
Humans
Middle Aged
NF-kappa B genetics
NF-kappa B metabolism
Receptors, CXCR4 genetics
Signal Transduction drug effects
Smoothened Receptor genetics
Smoothened Receptor metabolism
Curcumin therapeutic use
Doxorubicin therapeutic use
Drug Therapy, Combination methods
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4978
- Volume :
- 44
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular biology reports
- Publication Type :
- Academic Journal
- Accession number :
- 28752270
- Full Text :
- https://doi.org/10.1007/s11033-017-4115-2