Total Saponins of Rubus Parvifolius L. Exhibited Anti-Leukemia Effect in vivo through STAT3 and eIF4E Signaling Pathways / 中国结合医学杂志

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 signifificant inhibitory effect on tumor formation. The nude mice treated with TSRP showed a signifificant 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 eIF4E 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.

Rubus parvifolius L. inhibited the growth of leukemia K562 cells in vitro and in vivo / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the antiproliferative activity of Rubus parvifolius L. (RP) extract, its medicinal serum and RP total saponins (RPTS) against K562 cells in vitro and in vivo.</p><p><b>METHODS</b>Nude mice models bearing leukemia tumors were treated with different concentrations of RP extract. The size, weight and histopathological change of leukemic tumors were determined. Semi-solid agar culture and methylthiazolyl tetrazolium (MTT) assay were used to determine in vitro the inhibition of colony formation and proliferation of K562 cells respectively by different concentrations of RP medicinal serum and RPTS.</p><p><b>RESULTS</b>RP extract had a tumor inhibition rate of 84.8% when administered to mice at a dose of 1.0 g/day of crude RP root equivalent. Semi-solid agar culture of K562 cells in the presence of 20% (v/v) of RP medicinal serum and 150 mg/L RPTS demonstrated a 50.8% and 100% inhibition of the colony forming unit (CFU)-K562, respectively. The same doses of RP medicinal serum and RPTS showed a proliferation inhibition of 31.4% and 86.3%, respectively against K562 cells in MTT assay.</p><p><b>CONCLUSION</b>RP extract and RPTS show effective antiproliferative activity against myeloid leukemia cells in vitro and in vivo.</p>