Cisplatin prevents breast cancer metastasis through blocking early EMT and retards cancer growth together with paclitaxel
نویسندگان
چکیده
Cancer growth is usually accompanied by metastasis which kills most cancer patients. Here we aim to study the effect of cisplatin at different doses on breast and metastasis. Methods We used treat cells, then detected migration cells changes epithelial-mesenchymal transition (EMT) markers assay, Western blot, immunofluorescent staining. Next, analyzed RNA expression genes RNA-seq confirmed binding activating transcription factor 3 (ATF3) cytoskeleton related ChIP-seq. Thereafter, combined paclitaxel in a neoadjuvant setting xenograft mouse models. Furthermore, association disease prognosis with cytoskeletal ATF3 clinical data analysis. Results When administered higher dose (6 mg/kg), inhibits both metastasis, yet strong side effects, whereas lower (2 mg/kg) blocks without obvious killing effects. Cisplatin through blocking early steps EMT. It antagonizes transforming beta (TGFb) signaling suppressing many involved reorganization filopodia formation occur EMT are responsible for Mechanistically, TGFb fibronectin-1 (FN1) constitute positive reciprocal regulation loop that critical TGFb/SMAD3 signaling, repressed induced ATF3. administration 2 mg/kg conjunction causing effects inhibiting colonization target organs. Conclusion Thus, prevents EMT, combination represents promising therapy tumor
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ژورنال
عنوان ژورنال: The FASEB Journal
سال: 2021
ISSN: ['0892-6638', '1530-6860']
DOI: https://doi.org/10.1096/fasebj.2021.35.s1.05167