Total Saponins of Rubus Parvifolius L.Exhibited Anti-Leukemia Effect in vivo through STAT3 and eIF4E

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Objective:To investigate the anti-leukemia effect of total saponins of Rubus parvifolius L.(TSRP) on K562 cell xenografts in nude mice and the mechanisms of action.Methods:The K562 cell xenografts in nude mice were established,and then randomly divided into 5 groups,the control group,the cytosine arabinoside group(Ara-c) and 3 TSRP groups (20,40 and 100 mg/kg).The tumor volume and mass of each group of nude mice were measured and the anti-tumor rates of TSRP were calculated subsequently.The apoptosis status of tumor cells was detected by hematoxylin-eosin (HE) and terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining analysis.Finally,the activities of apoptosis related signaling of signal transducer and activator of transcription 3 (STAT3),eukaryotic initiation factor 4E (eIF4E) and B-cell lymphoma-2 (bcl-2) were determined with immunohistochemistry tests.Results:Subcutaneous injection of K562 cells induced tumor formation in nude mice,and the TSRP treated group showed a significant inhibitory effect on tumor formation.The nude mice treated with TSRP showed a significant decrease in tumor growth rate and tumor weight in comparison to the control group (all P<0.05).The HE staining and TUNEL assay showed that TSRP induced cell death by apoptosis.The immunohistochemical assay showed down-regulation of the bcl-2 gene in the TSRP treated cells.The phosphorylation levels of elF4E and STAT3 were decreased obviously after the treatment of TSRP.Conclusion:TSRP had an excellent tumor-suppressing effect on K562 cells in the nude mice xenograft model,suggesting that TSPR can be developed as a promising anti-chronic myeloide leukemia drug.
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