Doxorubicin effect is enhanced by sphingosine-1-phosphate signaling antagonist in breast cancer

The Journal of Surgical Research
Eriko KatsutaK Takabe

Abstract

Doxorubicin is one of the most commonly used chemotherapeutic drugs for breast cancer; however, its use is limited by drug resistance and side effects. We hypothesized that adding FTY720, a sphingosine-1-phosphate (S1P) receptor functional antagonist, to doxorubicin would potentiate its effects by suppression of drug-induced inflammation. The Cancer Genome Atlas, Gene Expression Omnibus data sets, and National Cancer Institute-60 panel were used for gene expressions and gene set enrichment analysis. E0771 syngeneic mammary tumor cells were used. OB/OB mice fed with western high-fat diet were used as an obesity model. STAT3 expression was significantly increased after doxorubicin treatment in human breast cancer that implicates that doxorubicin evokes inflammation. Expression of sphingosine kinase 1, the enzyme that produces S1P and links inflammation and cancer, tended to be higher in doxorubicin-resistant human cancer and cell lines. In a murine breast cancer model, sphingosine kinase 1, S1P receptor 1, interleukin 6, and STAT3 were overexpressed in the doxorubicin-treated group, whereas all of them were significantly suppressed with addition of FTY720. Combination therapy synergistically suppressed cancer growth both in vitro...Continue Reading

Citations

Sep 5, 2017·International Journal of Molecular Sciences·Nahal HaddadiEileen M McGowan
Jun 4, 2020·International Journal of Molecular Sciences·Eriko KatsutaKazuaki Takabe
Sep 17, 2020·International Journal of Molecular Sciences·Masanori OshiKazuaki Takabe
Apr 9, 2020·Frontiers in Oncology·Heba AlshakerDmitri Pchejetski
Jul 18, 2018·Oxidative Medicine and Cellular Longevity·Márcia Fernanda Correia Jardim PazJuliana da Silva
Jan 8, 2020·International Journal of Molecular Sciences·Eriko KatsutaKazuaki Takabe

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