Tanshinone IIA potentiates the efficacy of imatinib by regulating the AKT‑MDM2‑P53 signaling pathway in Philadelphia chromosome‑positive acute lymphoblastic leukemia

Guo,Yong; Wang,Fang-Fang; Xiang,Bing; Ma,Hong-Bing; Gong,Yu-Ping

doi:10.3892/ol.2021.13125

Tanshinone IIA potentiates the efficacy of imatinib by regulating the AKT‑MDM2‑P53 signaling pathway in Philadelphia chromosome‑positive acute lymphoblastic leukemia

Authors:
- Yong Guo
- Fang-Fang Wang
- Bing Xiang
- Hong-Bing Ma
- Yu-Ping Gong
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Affiliations: Department of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China, Hematology Research Laboratory, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: November 8, 2021 https://doi.org/10.3892/ol.2021.13125
Article Number: 7
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Philadelphia chromosome‑positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by breakpoint cluster region‑abelson leukemia virus (BCR/ABL) kinase. Targeting BCR/ABL kinase with tyrosine kinase inhibitors combined with chemotherapy is the standard first‑line therapy for Ph+ ALL. Imatinib and dasatinib are the preferred agents for the treatment of Ph+ ALL. Dasatinib treatment can induce a faster and deeper remission than imatinib treatment; however, the side effects of dasatinib, especially the cardiovascular side effects, are markedly greater than those of imatinib. Patients will benefit from treatments that improve the efficacy of imatinib without increasing its side effects. The present study revealed that tanshinone IIA markedly potentiated the cytotoxic and apoptotic induction effects of imatinib by regulating the AKT‑MDM2‑P53 signaling pathway and inhibiting the anti‑apoptotic proteins BCL2 and MCL1 apoptosis regulator, BCL2 family member in Ph+ ALL cell lines. In vitro studies, MTT assay, flow cytometry, western blotting and reverse transcription‑quantitative PCR were performed in the present study to detect cell viability, cell apoptosis, protein expression and gene expression, respectively. In a Ph+ ALL mouse model, imatinib combined with tanshinone IIA also exhibited a synergistic effect on the reduction in leukemia burden without increasing the toxic side effects of imatinib. These results demonstrated that imatinib combined with tanshinone IIA might be a promising treatment strategy for patients with Ph+ ALL.

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