Targeting ATM Enhances Triple Negative Breast Cancer Response to Chemotherapy

[Speaker] Rong Xu:1
[Co-author] Hancheng Mei:1, Lin Zhu:1, Jiaxiong Ming:1, Zhaocong Wang:1, Hui Chen:1, Haifa Shen:2,3
1:Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, China, 2:Department of Nanomedicine, Houston Methodist Research Institute, USA, 3:Department of Cell and Developmental Biology, Weill Cornell Medicine, USA

Breast cancer is the most common cancer in women worldwide and poses a big health threat. Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and poor prognosis after chemotherapy resistance. Ataxia telangiectasia mutated (ATM) is recruited and activated by chemotherapy induced DNA double strand breaks and is a central regulator of DNA damage response. Revealing the effects and mechanisms of ATM in chemotherapy resistance is very important for breast cancer treatment. In the present study, we found that inhibition of ATM with gene specific siRNA could enhance TNBC response to chemotherapy, and the response might be related to ATM regulation of Stat3, Akt, Catenin, Bcl-2 and survivin expression. We applied liposomal encapsulated, porous silicon based multistage vector delivery system (MSV) to deliver ATM siRNA to TNBC xenograft tumors in nude mice, and found that knockdown of ATM expression could enhance inhibitory effect of doxorubicin on tumor growth and tumor cell apoptosis. These results confirm ATM as a potential TNBC treatment target.
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