Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy.
Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy.
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DOI：
10.2741/e55
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
R. Sahu;M. Epperly;S. Srivastava
中科院分区：
文献类型：
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作者：
R. Sahu;M. Epperly;S. Srivastava
全身毒性和耐药性的增加是胰腺癌放射治疗的主要缺点。我们之前已经证明BITC可以抑制人胰腺癌细胞的生长并诱导细胞凋亡。在这里，我们确定了BITC是否能使BxPC-3细胞增敏，并增加γ辐照的治疗潜力。细胞用2.5微米的BITC预处理24小时，然后暴露于5 Gy的γ辐照下，再生长24或48小时，然后进行分析。与单独暴露于γ辐照的细胞相比，BITC和γ辐照联合使用显著降低了细胞的存活率，并显著增强了细胞在G2/M期的停滞。G2/M阻滞与DNA损伤相关，导致ATR （Ser-428）、Chk2 （Thr-68）、Cdc25C （Ser-216）、Cdk-1 （Tyr-15）磷酸化，并诱导p21Waf1/Cip1。而联合用药48 h后，BxPC-3细胞凋亡增加2.8倍。48 h凋亡与NF-kappa B抑制和p38激活有关。综上所述，本研究结果表明，btc可增强γ辐照诱导细胞凋亡的作用。
Increase in systemic toxicity and resistance are the major drawbacks of radiation therapy in the treatment of pancreatic cancer. We have shown previously that BITC inhibits the growth of human pancreatic cancer cells and induces apoptosis. Here we determined whether BITC could sensitize BxPC-3 cells and increase the therapeutic potential of gamma-irradiation. Cells were pretreated with 2.5 microM BITC for 24h followed by exposure to 5 Gy of gamma-irradiation and were allowed to grow for another 24 or 48 h before being analyzed. Combination of BITC and gamma-irradiation significantly reduced survival of cells and caused significantly enhanced arrest of cells in G2/M phase as compared to cells exposed to gamma-irradiation alone. G2/M arrest was associated with DNA damage leading to the phosphorylation of ATR (Ser-428), Chk2 (Thr-68), Cdc25C (Ser-216), Cdk-1 (Tyr-15) and induction of p21Waf1/Cip1. However, combination treatment after 48 h caused 2.8-fold increase in apoptosis in BxPC-3 cells. Apoptosis at 48 h was associated with NF-kappa B inhibition and p38 activation. Taken together, results of the present study suggest that the apoptosis-inducing effect of gamma-irradiation can be increased by BITC.