• Am. J. Chin. Med. · Jan 2023

    Dihydroartemisinin Affects STAT3/DDA1 Signaling Pathway and Reverses Breast Cancer Resistance to Cisplatin.

    • Jing Zhang, Yang Li, Ji-Guo Wang, Jing-Yu Feng, Guo-Dong Huang, and Chang-Guo Luo.
    • The First School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.
    • Am. J. Chin. Med. 2023 Jan 1; 51 (2): 445459445-459.

    AbstractDihydroartemisinin (DHA) has anticancer effects on multiple tumors, including those associated with breast cancer. This study aimed to investigate the mechanism causing DHA-reversing cisplatin (DDP) resistance in breast cancer. Relative mRNA and protein levels were tested using a qRT-PCR and western blot assay. Cell proliferation, viability, and apoptosis were evaluated using colony formation, MTT, and flow cytometry assays, respectively. Interaction of STAT3 and DDA1 was measured via a dual-luciferase reporter assay. The results showed that DDA1 and p-STAT3 levels were dramatically elevated in DDP-resistant cells. DHA treatment repressed proliferation and induced apoptosis of DDP-resistant cells by suppressing STAT3 phosphorylation; the inhibition ability was positively proportional to the DHA concentration. DDA1 knockdown inhibited cyclin expression, promoted G0/G1 phase arrest, restrained cell proliferation, and induced apoptosis of DDP-resistant cells. Furthermore, knockdown of STAT3 restrained proliferation and induced apoptosis and G0/G1 cell cycle arrest of DDP-resistant cells by targeting DDA1. DHA could restrain tumor proliferation of breast cancer via enhancing drug sensitivity of DDP-resistant cells through the STAT3/DDA1 signaling pathway.

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