Abstract
Overexpression of Sonic Hedgehog signaling (Shh) pathway molecules is associated with invasiveness and recurrence in breast carcinoma. Therefore, inhibition of the Shh pathway downstream molecule Glioma-associated Oncogene Homolog (Gli) was investigated for its ability to reduce progression and invasiveness of patient-derived breast cancer cells and cell lines. Human primary breast cancer T2 cells with high expression of Shh signaling pathway molecules were compared with breast cancer line MDA-MB-231 cells. The therapeutic effects of Gli inhibitors were examined in terms of the cell proliferation, apoptosis, cancer stem cells, cell migration and gene expression. Blockade of the Shh signaling pathway could reduce cell proliferation and migration only in MDA-MB-231 cells. Hh pathway inhibitor-1 (HPI-1) increased the percentages of late apoptotic cells in MDA-MB-231 cells and early apoptotic cells in T2 cells. It reduced Bcl2 expression for cell proliferation and increased Bim expression for apoptosis. In addition, Gli inhibitor HPI-1 decreased significantly the percentages of cancer stem cells in T2 cells. HPI-1 worked more effectively than GANT-58 against breast carcinoma cells. In conclusion, HPI-1 could inhibit cell proliferation, reduce cell invasion and decrease cancer stem cell population in breast cancer cells. To target Gli-1 could be a potential strategy to suppress breast cancer stem cells.
Highlights
Breast carcinoma is the most common cancer among women worldwide [1,2]
T2 cells can form a bigger spheroid than MDA-MB-231 cells does in 3-dimensional culture (Figure 1b)
Breast carcinoma T2 cells were isolated from a patient with estrogen receptor (ER) (−), progesterone receptor (PR) (−) and Her2 (+)
Summary
Breast carcinoma is the most common cancer among women worldwide [1,2]. The current main treatments include surgery, radiation, chemotherapy, hormone therapy and target therapy [3,4]. Metastases at distant sites and recurrence are the main causes of death in breast cancer. Breast cancer stem cells (CSC) CD44+CD24low exhibit enhanced invasive properties for the metastasis and escape from the therapies [5,6]. Targeting CSC could be a strategy to prevent metastasis and recurrence. The Sonic Hedgehog signaling (Shh) pathway plays an essential role in maintaining cancer stem cells and side populations [7,8]. This pathway is involved in breast carcinogenesis, invasion and metastasis [9,10,11,12]. Our previous study suggested overexpression of Hh signaling pathway molecules
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
