Apigenin promotes apoptosis of 4T1 cells through PI3K/AKT/Nrf2 pathway and improves tumor immune microenvironment in vivo

Author:

Zhang Chu12,Liao Yupei12,Li Tangjia12,Zhong Haijing12,Shan Luchen12,Yu Pei12,Xia Chenglai34,Xu Lipeng12ORCID

Affiliation:

1. Institute of New Drug Research , College of Pharmacy/Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases/International Cooperative Laboratory of Traditional Chinese, Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, , Guangzhou 510632 , China

2. Jinan University , College of Pharmacy/Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases/International Cooperative Laboratory of Traditional Chinese, Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, , Guangzhou 510632 , China

3. Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University , Foshan 528000 , China

4. School of Pharmaceutical Sciences, Southern Medical University , Guangzhou 510515 , China

Abstract

Abstract The 2022 US Cancer Statistics show that breast cancer is one of the most common cancers in women. Epidemiology has shown that adding flavonoids to the diet inhibits cancers that arise in particular women, such as cervical cancer, ovarian cancer, and breast cancer. Although there have been research reports on apigenin (API) and breast cancer, its anti-tumor effect and potential mechanism on breast cancer have not yet been clarified. Therefore, in this study, we used 4T1 cells and a 4T1 xenograft tumor mouse model to investigate the antitumor effect of API on breast cancer and its underlying mechanism. In vitro, we used MTT, transwell, staining, and western blotting to investigate the inhibitory effect of apigenin on 4T1 and the underlying molecular mechanism. In vivo by establishing a xenograft tumor model, using immunohistochemistry, and flow cytometry to study the inhibitory effect of apigenin on solid breast tumors and its effect on the tumor immune microenvironment. The results showed that API can induce breast cancer cell apoptosis through the PI3K/AKT/Nrf2 pathway and can improve the tumor immune microenvironment in mice with breast tumors, thereby inhibiting the growth of breast cancer. Thus, API may be a promising agent for breast cancer treatment.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

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