Efficacy of the hypoxia-activated prodrug evofosfamide (TH-302) in nasopharyngeal carcinoma in vitro and in vivo

Cancer Communications
Yan HuangLi Zhang

Abstract

Tumor hypoxia is considered an important factor in metastasis and disease relapse. Evofosfamide is a hypoxia-activated prodrug that selectively targets the hypoxic regions of solid tumors. As hypoxia-inducible factor-1α (HIF-1α) is overexpressed in nasopharyngeal carcinoma (NPC) tissues, we performed the present study to evaluate the efficacy profile of evofosfamide in NPC. We evaluated the efficacy of evofosfamide as a single agent or combined with cisplatin (DDP) in the NPC cell lines CNE-2, HONE-1 and HNE-1, and in nude mouse xenograft tumor models. Evofosfamide exhibited hypoxia-selective cytotoxicity in NPC cell lines, with 50% inhibition concentration (IC50) values of 8.33 ± 0.75, 7.62 ± 0.67, and 0.31 ± 0.07 μmol/L under hypoxia in CNE-2, HONE-1 and HNE-1 cells, respectively. The sensitization ranged from ninefold to greater than 300-fold under hypoxia compared with normoxia controls. The combination of evofosfamide with DDP had a synergistic effect on cytotoxicity in the NPC cell lines by combination index values assessment. Cell cycle G2 phase was arrested after treated with 0.05 μmol/L evofosfamide under hypoxia. Histone H2AX phosphorylation (γH2AX) (a marker of DNA damage) expression increased while HIF-1α expression...Continue Reading

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Citations

Aug 9, 2019·Cancer Chemotherapy and Pharmacology·J DelahousseA Paci
Oct 24, 2020·Signal Transduction and Targeted Therapy·Yuanbo KangLei Wang
Apr 17, 2021·Critical Reviews in Oncology/hematology·Nalini DevarajanSenthil Kumar Ganesan
May 7, 2021·Frontiers in Pharmacology·Yue LiXiao-Feng Li
Aug 17, 2021·Frontiers in Oncology·Yue LiXiao-Feng Li

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Methods Mentioned

BETA
flow cytometry
electrophoresis
xenograft
xenografts

Software Mentioned

Calcusyn
CELL Quest
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