The radiosensitizing effect of fluorocyclopentenyl-cytosine (RX-3117) in ovarian and lung cancer cell lines

被引：3
|
作者：
Sarkisjan, Dzjemma [1 ]
van den Berg, Jaap [2 ]
Smit, Evelyn [1 ]
Lee, Young B. [3 ]
Kim, Deog J. [3 ]
Peters, Godefridus J. [1 ]
机构：
[1] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, Dept Radio Therapy, Amsterdam, Netherlands
[3] Rexahn Pharmaceut Inc, Rockville, MD USA
来源：
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2016年 / 35卷 / 10-12期
关键词：
RX-3117; cytidine analog; radiosensitizing effect; DNA damage; cell cycle proteins; GROWTH-FACTOR RECEPTOR; CHEMOTHERAPEUTIC-AGENTS; ANTITUMOR-ACTIVITY; IN-VIVO; GEMCITABINE; AZACITIDINE; MECHANISM; DNA; 2'; 2'-DIFLUORO-2'-DEOXYCYTIDINE; 5-AZACYTIDINE;
D O I：
10.1080/15257770.2016.1216565
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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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收藏
页码：619 / 630
页数：12
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