Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic conditionReport as inadecuate




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We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α HIF-1α, and that the hypoxia-activated prodrug TH-302 inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin DOX-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 ABCB1, ATP-binding cassette transporter G2 ABCG2, platelet-derived growth factor PDGF, vascular endothelial growth factor VEGF, and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.



Author: Hiroki Yamazaki, Yu-Chang Lai, Morihiro Tateno, Asuka Setoguchi, Yuko Goto-Koshino, Yasuyuki Endo, Munekazu Nakaichi, Hajime Tsuj

Source: http://plos.srce.hr/



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