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- Title
Dihydroartemisinin Affects STAT3/DDA1 Signaling Pathway and Reverses Breast Cancer Resistance to Cisplatin.
- Authors
Zhang, Jing; Li, Yang; Wang, Ji-Guo; Feng, Jing-Yu; Huang, Guo-Dong; Luo, Chang-Guo
- Abstract
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.
- Subjects
PROTEIN analysis; REVERSE transcriptase polymerase chain reaction; FLOW cytometry; WESTERN immunoblotting; ANTINEOPLASTIC agents; APOPTOSIS; CELL cycle proteins; CELLULAR signal transduction; CELL survival; CISPLATIN; MESSENGER RNA; CELL proliferation; BACTERIAL growth; MICROBIOLOGICAL techniques; TUMOR markers; CELL lines; COLORIMETRY; DRUG resistance in cancer cells; BREAST tumors; PHOSPHORYLATION; PHARMACODYNAMICS
- Publication
American Journal of Chinese Medicine, 2023, Vol 51, Issue 2, p445
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X23500234