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.
引用
收藏
页码：619 / 630
页数：12
相关论文
共 50 条
  • [41] Endostatin exerts radiosensitizing effect in non-small cell lung cancer cells by inhibiting VEGFR2 expression
    Liu, L.
    Qiao, Y.
    Hu, C.
    Liu, Y.
    Xia, Y.
    Wang, L.
    Liu, B.
    Chen, H.
    Jiang, X.
    CLINICAL & TRANSLATIONAL ONCOLOGY, 2016, 18 (01): : 18 - 26
  • [42] Effect of AURKA Gene Expression Knockdown on Angiogenesis and Tumorigenesis of Human Ovarian Cancer Cell Lines
    Cong Wang
    Qin Yan
    Minmin Hu
    Di Qin
    Zhenqing Feng
    Targeted Oncology, 2016, 11 : 771 - 781
  • [43] Effect of paclitaxel (Taxol(R)) on CA 125 expression and release by ovarian cancer cell lines
    Bonfrer, JMG
    Linders, C
    Hageman, PC
    Hilkens, JGW
    Korse, CM
    Molthoff, CFM
    TUMOR BIOLOGY, 1997, 18 (04) : 232 - 240
  • [44] Sensitization of ovarian cancer cell lines to cisplatin by MMP-9 inhibitor: a hormetic effect
    Laios, A.
    O'Toole, S. A.
    Bashir, M.
    Flavin, R.
    Kelly, L.
    D'Arcy, T.
    Gleeson, N.
    Sheppard, B.
    Sheils, O.
    O'Leary, J. J.
    IRISH JOURNAL OF MEDICAL SCIENCE, 2010, 179 : S55 - S55
  • [45] Effect of AURKA Gene Expression Knockdown on Angiogenesis and Tumorigenesis of Human Ovarian Cancer Cell Lines
    Wang, Cong
    Yan, Qin
    Hu, Minmin
    Qin, Di
    Feng, Zhenqing
    TARGETED ONCOLOGY, 2016, 11 (06) : 771 - 781
  • [46] Pentoxifylline potentiates the antitumor effect of cisplatin and etoposide on human lung cancer cell lines
    Ohsaki, Y
    Ishida, S
    Fujikane, T
    Kikuchi, K
    ONCOLOGY, 1996, 53 (04) : 327 - 333
  • [47] Inhibitory effect of adenovirus-uteroglobin transduction on the growth of lung cancer cell lines
    Jae Cheol Lee
    Kyung-Ho Park
    Seon Jin Han
    Chul-Gyu Yoo
    Choon-Taek Lee
    Sung Koo Han
    Young-Soo Shim
    Young Whan Kim
    Cancer Gene Therapy, 2003, 10 : 287 - 293
  • [48] Inhibitory effect of adenovirus-uteroglobin transduction on the growth of lung cancer cell lines
    Lee, JC
    Park, KH
    Han, SJ
    Yoo, CG
    Lee, CT
    Han, SK
    Shim, YS
    Kim, YW
    CANCER GENE THERAPY, 2003, 10 (04) : 287 - 293
  • [49] The effect of methylene blue in the photodynamic therapy on A549 lung cancer cell lines
    Oak, Chul Ho
    Jang, Tae Won
    Kim, Young Ho
    Jung, Maan Hong
    EUROPEAN RESPIRATORY JOURNAL, 2012, 40
  • [50] Effect of FK866, NAMPT inhibitor, on small cell lung cancer cell lines.
    Desautels, Danielle Nicole
    Bourrier, Mathieu
    Peltier, Cheryl
    Banerji, Versha
    Banerji, Shantanu Otto
    JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (15)
12345