10.6084/M9.FIGSHARE.19448344
Ruixin Gu
Ruixin
Gu
Wei Zhang
Wei
Zhang
Dandan Xu
Dandan
Xu
Stachydrine is effective and selective against blast phase chronic myeloid leukaemia through inhibition of multiple receptor tyrosine kinases
<p>Resistance to BCR-ABL tyrosine kinase inhibitor (TKI) is the cause of treatment failure in blast phase chronic myeloid leukaemia (BP-CML). Agents that act synergistically with BCR-ABL TKI are required to improve response.</p> <p>This work investigated the effects of stachydrine in CML.</p> <p>CML cells were treated with control or stachydrine at 20, 40 and 80 µM. Proliferation and apoptosis were examined after 72 h treatment. Combination studies were performed in four groups: control, TKI, stachydrine and the combination of stachydrine and TKI. Immunoblotting analysis was performed in CML cells after 24 h treatment.</p> <p>Stachydrine inhibited K562 (IC<sub>50</sub> 61 µM), KCL22 (IC<sub>50</sub> 141 µM), LAMA84 (IC<sub>50</sub> 86 µM), Ba/F3 T315I (IC<sub>50</sub> 26 µM), Ba/F3 WT (IC<sub>50</sub> 22 µM) and KU812 (IC<sub>50</sub> 35 µM) proliferation, and induced apoptosis in these CML cell lines. Stachydrine significantly induced apoptosis, inhibited colony formation and self-renewal in BP-CML CD34<sup>+</sup> cells. The combination index of stachydrine and TKI combination was <1. Compared to TKI alone, the combination of stachydrine and TKI significantly induced more apoptosis and decreased colony formation in BP-CML CD34<sup>+</sup> cells. Stachydrine decreased phosphorylation levels of multiple receptor tyrosine kinases in CML cells.</p> <p>Our study is the first to demonstrate (1) the anticancer activity of stachydrine on primary patient cancer cells; (2) the inhibitory effects of stachydrine on cancer stem cells; (3) the synergism between stachydrine and other anticancer drugs.</p>
Biochemistry
Space Science
Microbiology
Cell Biology
Physiology
Pharmacology
Chemical Sciences not elsewhere classified
Developmental Biology
Cancer
Hematology
Taylor & Francis
2022
2022-03-29
2024-03-25
Journal contribution
15261184 Bytes
10.1080/13880209.2022.2044862
CC BY 4.0