Abstract
Breast carcinoma is the most common female cancer with considerable metastatic potential. Discovery of new therapeutic approaches for treatment of metastatic breast cancer is still needed. Here, we reported our finding with niclosamide, an FDA approved anthelmintic drug. The potency of niclosamide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that niclosamide showed a dramatic growth inhibition against breast cancer cell lines and induced apoptosis of 4T1 cells in a dose-dependent manner. Further, Western blot analysis demonstrated the occurrence of its apoptosis was associated with activation of Cleaved caspases-3, down-regulation of Bcl-2, Mcl-1 and Survivin. Moreover, niclosamide blocked breast cancer cells migration and invasion, and the reduction of phosphorylated STAT3Tyr705, phosphorylated FAKTyr925 and phosphorylated SrcTyr416 were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 20 mg/kg/d niclosamide suppressed 4T1 tumor growth without detectable toxicity. Histological and immunohistochemical analyses revealed a decrease in Ki67-positive cells, VEGF-positive cells and microvessel density (MVD) and an increase in Cleaved caspase-3-positive cells upon niclosamide. Notably, niclosamide reduced the number of myeloid-derived suppressor cells (MDSCs) in tumor tissues and blocked formation of pulmonary metastases. Taken together, these results demonstrated that niclosamide may be a promising candidate for breast cancer.
Highlights
According to statistics, the three most commonly diagnosed types of cancer among women will be breast, lung and bronchus, and colorectum in the United States in 2013 [1]
In order to investigate whether niclosamide has direct effects on breast cancer cells, we tested the proliferation inhibition caused by niclosamide treatment on different breast cancer cell lines by MTT
Breast cancer is highly malignant with considerable metastatic potential, which urges to develop novel potential drug candidate to prevent tumor metastasis and treat tumor growth at present [34]
Summary
The three most commonly diagnosed types of cancer among women will be breast, lung and bronchus, and colorectum in the United States in 2013 [1]. About 64,640 cases of breast carcinoma in situ are expected to be newly diagnosed, and breast cancer is expected to account for 29% of all new carcinoma cases among women. Incidence rates are decreasing for all 4 major cancer sites (lung, colorectum, breast, and prostate) except female breast cancer, for which rates remained relatively stable from 2005 to 2009. Significant progress has been made in breast cancer detection and treatment, survival tends to be poorer in economically developing countries [4]. It is critical to develop novel therapeutic approaches for the treatment of breast cancer
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