The online version of this article (doi:10.1186/s12885-017-3250-4) contains supplementary material, which is available to authorized users.
Metastasis is the leading cause of death in breast cancer patients. CD73, also known as ecto-5′-nucleotidase, plays a critical role in cancer development including metastasis. The existing researches indicate that overexpression of CD73 promotes growth and metastasis of breast cancer. Therefore, CD73 inhibitor can offer a promising treatment for breast cancer. Here, we determined whether tiamulin, which was found to inhibit CD73, was able to suppress breast cancer development and explored the related mechanisms.
We firstly measured the effect of tiamulin hydrogen fumarate (THF) on CD73 using high performance liquid chromatography (HPLC). Then, we investigated cell proliferation, migration and invasion in MDA-MB-231 human breast cancer cell line and 4 T1 mouse breast cancer cell line treated with THF by migration assay, invasion assay and activity assay. Besides, we examined the effect of THF on syngeneic mammary tumors of mice by immunohistochemistry.
Our data demonstrated that THF inhibited CD73 by decreasing the activity instead of the expression of CD73. In vitro, THF inhibited the proliferation, migration and invasion of MDA-MB-231 and 4 T1 cells by suppressing CD73 activity. In vivo, animal experiments showed that THF treatment resulted in significant reduction in syngeneic tumor growth, microvascular density and lung metastasis rate.
Our results indicate that THF inhibits growth and metastasis of breast cancer by blocking the activity of CD73, which may offer a promising treatment for breast cancer therapy.
Additional file 1: Figure S1. The activity of CD73 was decreased by THF as well as APCP, but not by tylosin. a and b Effect of THF, APCP or tylosin on CD73 activity in breast cancer cells. CD73 activity was significantly decreased by THF or APCP, but not by tylosin in (a) MDA-MB-231 and (b) 4 T1 cells. Data represent the mean ± S.D. of three independent experiments. (*P < 0.05, **P < 0.01, ***P < 0.001 vs control). (PPTX 107 kb)12885_2017_3250_MOESM1_ESM.pptx
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- Tiamulin inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of CD73
- BioMed Central
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