FXR can slow proliferation of tamoxifen-resistant breast cancer cells: Study
January 24, 2016
1.MCF-7, which is sensitive to tamoxifen; that is, tamoxifen keeps these cancer cells in check2.MCF-7TR, which is resistant to tamoxifen; that is, the drug does not keep the cancer in check.
The research team activated FXR with either a bile acid, chenodeoxycholic acid, or a synthetic, GW4064. Once FXR was activated, the researchers found that it reduced the survivability of both the tamoxifen-sensitive and tamoxifen-resistant cells. In fact, FXR inhibited the tamoxifen-resistant cancer cells (MCF-7TR) more than the tamoxifen sensitive cells.
How does it work?The researchers found that FXR inhibited expression of a growth factor signaling mediator -- human epidermal growth factor receptor 2 (HER2). HER2 is present in 20% of breast cancers and is associated with enhanced malignancy and poorer prognosis. The over-expression of HER2 on the breast cancer cell surface is believed to disrupt the cell's ability to control growth, Giordano said, allowing the cells to rapidly proliferate. FXR seems to inhibit that process.
Why would FXR work better against MCF-7TR, the tamoxifen-resistant cells? Part of the explanation may be that MCF-7TR relies more on HER2, and FXR targets HER2, Giordano said. That would make the tamoxifen-resistant cancer cells more vulnerable to activated FXR, she said.
"This is an 'in vitro' preclinical study, but of course the next step will be to test this in vivo using mice implanted with tamoxifen-resistant breast cancer cells," said Giordano.
SOURCE American Society for Investigative Pathology