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The combination of methylsulfonylmethane and tamoxifen inhibits theJak2/STAT5b pathway and synergistically inhibits tumor growth andmetastasis in ER-positive breast cancer xenografts
- Source :
- BMC CANCER(15), BMC Cancer
- Publication Year :
- 2015
-
Abstract
- Background Combination therapy, which reduces the dosage intensity of the individual drugs while increasing their efficacy, is not a novel approach for the treatment of cancer. Methylsulfonylmethane (MSM) is an organic sulfur compound shown to act against tumor cells. Tamoxifen is a commercially available therapeutic agent for breast malignancies. Methods In the current study, we analyzed the combinatorial effect of MSM and tamoxifen on the suppression of ER-positive breast cancer xenograft growth and metastasis. Additionally, we also validated the molecular targets by which the drug combination regulated tumor growth and metastasis. Results We observed that the combination of MSM and tamoxifen regulated cell viability and migration in vitro. The intragastric administration of MSM and subcutaneous implantation of tamoxifen tablets led to tumor growth suppression and inhibition of the Janus kinase 2 (Jak2)/signal transducer and activator of transcription 5b (STAT5b) pathway. Our study also assessed the regulation of signaling molecules implicated in the growth, progression, differentiation, and migration of cancer cells, such as Jak2, STAT5b, insulin-like growth factor-1Rβ, and their phosphorylation status. Conclusions Study results indicated that this combination therapy inhibited tumor growth and metastasis. Therefore, this drug combination may have a synergistic and powerful anticancer effect against breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1445-0) contains supplementary material, which is available to authorized users.
- Subjects :
- Cancer Research
medicine.medical_specialty
Combination therapy
Estrogen receptor
Breast Neoplasms
Breast cancer
Methylsulfonylmethane
Tamoxifen
Jak2/STAT5b pathway
Xenograft
Metastasis
Internal medicine
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
Genetics
medicine
STAT5 Transcription Factor
Humans
Dimethyl Sulfoxide
Sulfones
Neoplasm Metastasis
Cell Proliferation
Janus kinase 2
biology
business.industry
Estrogen Receptor alpha
Cancer
Receptors, Somatomedin
Janus Kinase 2
medicine.disease
Xenograft Model Antitumor Assays
Endocrinology
Oncology
Cancer cell
biology.protein
Cancer research
Female
business
medicine.drug
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- BMC CANCER(15), BMC Cancer
- Accession number :
- edsair.doi.dedup.....88549d1e06be9a4cda11d8e2951209e5