Thompson Lab’s collaboration with Nanjing Medical University in China leads to a new publication in Journal of Experimental & Clinical Cancer Research.
Date Posted: lunes, diciembre 02, 2019
Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells
Tamoxifen, an estrogen receptor (ER) antagonist, is widely used for first line adjuvant endocrine therapy against ER-positive breast cancer. Although it substantially reduces recurrence and mortality rates in ER-positive breast cancer patients, with 5 years of tamoxifen therapy, most initially responsive patients experience a recurrence, and the tumors eventually become resistant to tamoxifen. In this paper, we show that protein arginine deiminase 2 (PAD2) is significantly upregulated in tamoxifen-resistant breast cancer cells, i.e. MCF7/TamR. Interestingly, depletion of PAD2 or inhibition of PAD2 with a pan PAD inhibitor (Cl-amidine) increases the sensitivity of MCF7/TamR cells to tamoxifen. We also show that Cl-amidine treatment enhances the efficacy of docetaxel, a second generation taxane-based chemotherapeutic agent, on tamoxifen-resistant breast cancer cells. Altogether, these results suggest that PAD2 functions as a biomarker for tamoxifen-resistant breast cancers and inhibiting PAD2 combined with docetaxel may offer a new approach to treat such kind of cancers.
Figure. (A) Endogenous PAD1–4 mRNA levels in MCF7/TamR cells. TamR and TamS stand for tamoxifen-resistant and -sensitive MCF7 cells, respectively. (B) Mice bearing PAD2 knockdown cells exhibited smaller tumors than mice with shRNA control cells post-tamoxifen treatment (n = 3/group). (C) Flow cytometric analysis of 0.1 μM docetaxel and 25 μM Cl-amidine show that this combination accelerates the apoptosis of MCF7/TamR cells compared to either individual treatment.
Read the full article: https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1404-8
For more about the Thompson lab, please visit https://www.umassmed.edu/thompson
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