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

• Published in: The American journal of Chinese medicine (1979) Vol. 51; no. 2; p. 445
• Main Authors: Zhang, Jing, Li, Yang, Wang, Ji-Guo, Feng, Jing-Yu, Huang, Guo-Dong, Luo, Chang-Guo
• Format: Journal Article
• Language: English
• Published: Singapore 2023
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - genetics; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cell Line, Tumor; Cell Proliferation; Cisplatin - pharmacology; Drug Resistance, Neoplasm - genetics; Female; Humans; MicroRNAs - metabolism; Ovarian Neoplasms - drug therapy; Signal Transduction - genetics; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; DDP; Dihydroartemisinin (DHA); Breast Cancer; STAT3; DDA1
• ISSN: 1793-6853
• DOI: 10.1142/S0192415X23500234

Dihydroartemisinin (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.