Bio: Dr. Feng is a professor at School of Public Health of Shandong University. Under the support of several National Natural Science Foundation of China, her research is focused on the study of the genotoxicity of radiation injury. Her research work has been published in international academic journals such as PNAS. NAR and CDD.

Abstract: Radiotherapy (RT) is one of the important treatment methods for breast cancer patients. RT can directly kill tumor tissues, which called the targeted effect. However, some patients may be resistant to RT treatment; moreover, RT can also cause systemic side effects, such as gastrointestinal reactions, hematopoietic dysfunction and fibrosis, which is called the non-targeted effect of radiation. Thus, it has been proposed whether there is a chemical agent that can not only improve RT efficiency as a tumor radiosensitizer but also reduce side effects as a protector. In this study we focused on two chemicals: valproic acid (VPA) and VPA derivative (HPTA), and used established carcinogens (DMBA)-induced human normal breast cell transformed cells and DMBA-induced breast cancer animal models to test our hypothesis. It was found that for tumors, two chemicals act as DNA damage repair inhibitors to increase Rad51-UB and reduce Rad51 levels through upregulating ubiquitination (Ub) enzyme-RFWD3 and downregulating deub enzyme-UCHL3 for improving radiosensitivity. However, for the non-targeted effect, two chemicals act as DNA damage repair protectants to reduce Rad51-UB and increase Rad51 levels by downregulating RFWD3 and upregulating UCHL3 for protecting normal tissues from radiation damage. VPA/HPTA can further activate M1 macrophage-CD8+T cell-mediated anti-tumor immunity in later period after RT treatment. Our conclusion is that VPA/HPTA has a dual effect, on the one hand, it acts as a radiosensitizer on tumor tissues through DNA repair inhibition and immune activation; and on the other hand, it acts as a radioprotector on normal tissues by enhancing DNA repair ability.

 References:

1. Benyu Su, David Lim , Chenyang Qi, Zhongwei Zhang, Junxiao Wang, Fengmei Zhang, Chao Dong, Zhihui Feng, VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU, Cell Death and Disease, (2023)14:114; 41419-023-05649-8. 

2. HDAC inhibitor HPTA initiates anti-tumor response by CXCL9/10-recruited CXCR3+CD4+T cells against PAHs carcinogenicity Chen Chen, David Lim, Zuchao Cai, Fengmei Zhang, Guochao Liu, Chao Dong, Zhihui Feng, Food and Chemical Toxicology 176 (2023) 113783.

3. Yisha Zhang, David Lim, Zuchao Cai, Junxuan Peng, Beidi Jia. Guoliang Chu, Fengmei Zhang, Zhihui Feng, Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages, Ecotoxicology and Environmental Safety, Volume 241, August 2022, 113779.

4. Zuchao Cai, David Lim, Guochao Liu, Chen Chen, Liya Jin, Wenhua Duan, Chenxia Ding, Qingjie Sun, Junxuan Peng, Chao Dong, Fengmei Zhang and Zhihui Feng. Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function, Frontiers in Immunology, 12 May 2021 646384.