期刊
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
卷 35, 期 10-12, 页码 619-630出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15257770.2016.1216565
关键词
RX-3117; cytidine analog; radiosensitizing effect; DNA damage; cell cycle proteins
资金
- Rexahn Pharmaceuticals, Inc.
RX-3117 (fluorocyclopentenyl-cytosine) is a novel cytidine analog currently being evaluated in a Phase Ib clinical trial in cancer patients with solid tumors. The radiosensitizing effect of RX-3117 was studied in A2780 ovarian cancer cells and non-small cell lung cancer cell lines and related to cell survival and the effect on cell cycle and cell cycle proteins. RX-3117 has a schedule-dependent radiosensitizing effect, but only at pre-incubation (dose modifying factors: 1.4-1.8), observed at pulse and fractionated irradiation. Radiosensitizion was also seen in a three-dimensional spheroid model. At the low radiosensitizing concentration, RX-3117 in combination with radiation led to an accumulation of cells in S-phase, which was accompanied with an increase of cell cycle proteins such as p-Chk2 and p-cdc25C. In addition, RX-3117 caused DNA damage and increased apoptosis. In conclusion, our in vitro experiments showed a radiosensitizing effect of RX-3117.
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