Gemcitabine Induces Radiosensitization Through Inhibition of RAD51-dependent Repair for DNA Double-strand Breaks.
Gemcitabine Induces Radiosensitization Through Inhibition of RAD51-dependent Repair for DNA Double-strand Breaks.
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发表时间：
2015-05
影响因子：
2
通讯作者：
Shinko Kobashigawa;K. Morikawa;H. Mori;G. Kashino
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作者：
Shinko Kobashigawa;K. Morikawa;H. Mori;G. Kashino
背景/目的吉西他滨（Gemcitabine，GEM）用于临床放化疗，但其增敏机制尚不完全清楚。我们评估了吉西他滨对胰腺癌细胞系放射增敏的作用。材料和方法使用胰腺细胞系PK-59和PK-45 p。在伽马辐照之前或之后给予总共5 μM GEM 4 h。结果GEM在放疗前对肿瘤细胞的杀伤作用有增强作用，而在放疗后对肿瘤细胞的杀伤作用无增强作用。我们重点研究了照射后RAD 51和磷酸化H2 AX灶的动态变化。照射后，在GEM预处理的细胞中观察到的磷酸-H2 AX灶的数量显著高于未处理的细胞。我们还发现GEM预处理抑制了RAD 51灶的形成和降解。GEM的放射增敏作用可通过敲低RAD 51而被抑制。结论RAD 51依赖性同源重组是GEM放射增敏作用的关键靶点之一。
BACKGROUND/AIM Gemcitabine (GEM) is used in clinical chemo-radiotherapy; however, the mechanism that contributes to enhanced radiosensitivity by GEM is not fully-understood. We evaluated the effect of GEM on radiosensitization in pancreatic cancer cell lines. MATERIALS AND METHODS Pancreatic cell lines PK-59 and PK-45p were used. A total of 5 μM GEM for 4 h were administered pre- or post-gamma irradiation. RESULTS Enhanced cell killing effects by GEM in radiotherapy were observed for pre-treatment but not post-treatment GEM. We focused on the dynamics of RAD51 and phospho-H2AX foci after irradiation. Significantly higher numbers of phospho-H2AX foci were observed in GEM pre-treated cells than in untreated cells after irradiation. We also found inhibition of the formation and degradation of RAD51 foci by GEM pre-treatment. The radiosensitizing effect of GEM was suppressed by knockdown of RAD51. CONCLUSION RAD51-dependent homologous recombination is one of the key targets in the GEM-induced radiosensitizing effect.