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Wang W.-Z.,Guangdong Province Key Laboratory of Pharmaceutical Bioactive Substances | Wang W.-Z.,Guangdong Pharmaceutical University | Pu Q.-H.,Guangdong Province Key Laboratory of Pharmaceutical Bioactive Substances | Pu Q.-H.,Guangdong Pharmaceutical University | And 11 more authors.
Leukemia Research | Year: 2015

BCR-ABL tyrosine kinase inhibitor imatinib fails to eradicate leukemia stem cells (LSCs), the underlying mechanisms maintaining CML LSCs remain poorly understood. Here, we showed that transient inhibition of miR-21 by antagomiR-21 markedly increased imatinib-induced apoptosis in CML, but not normal CD34+ stem/progenitor cells. Furthermore, PI3K inhibitors also significantly sensitized CML CD34+ cells to imatinib-induced apoptosis. MiR-21 or PI3K inhibitor in combination with imatinib treatment significantly decreased AKT phosphorylation and c-Myc expression than either agent did alone, but did not affect Bim and Bcl-6 expresssion. These findings indicate that miR-21 is required for maintaining the imatinib-resistant phenotype of CML CD34+ cells through PI3K/AKT signaling pathway, thus providing the basis for a promising therapeutic approach to eliminate CML LSCs. © 2015 Elsevier Ltd. Source

Jin X.-B.,Guangdong Pharmaceutical University | Jin X.-B.,Guangdong Province Key Laboratory of Pharmaceutical Bioactive Substances | Wang Y.-J.,Guangdong Pharmaceutical University | Wang Y.-J.,Guangdong Province Key Laboratory of Pharmaceutical Bioactive Substances | And 12 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Conventional chemotherapy against hepatocellular carcinoma typically causes various side effects. Our previous study showed that cecropin of Musca domestica can induce apoptosis in human hepatocellular carcinoma BEL-7402 cells in vitro. However, whether cecropin inhibits BEL-7402 cell in vivo and the question of possible side effects remained undentified. The present study confirmed tumor-inhibitory effects of cecropin in vivo, and furthermore strongly suggested that cecropin cytotoxicity in BEL-7402 cells in vivo may be mainly derived from its pro-apoptotic action. Specifically, we found that cecropin exerted no obvious side effects in tumor-bearing mice as it had no significant hematoxicity as well as visceral toxicity. Therefore, cecropin may be a potential candidate for further investigation as an antitumor agent against hepatocellular carcinoma. Source

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