United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA.
Int J Oncol. 2012 Apr;40(4):1277-84. doi: 10.3892/ijo.2011.1316. Epub 2011 Dec 22.
The efficacy of resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL SEM cell line. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, mice were injected intraperitoneally with resveratrol (10 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). Comparisons of the percent of human leukemia cells in blood and survival curves showed resveratrol did not inhibit progression of the disease. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed resveratrol was rapidly metabolized to glucuronidated and sulfated forms 1 h post-injection, with low to no resveratrol or metabolites observed in sera by 24-48 h. These data indicate that in contrast to findings in in vitro models, parenterally administered resveratrol does not have potential as a preventive agent against high risk t(4;11) ALL.
在经人源 t(4;11)急性淋巴细胞白血病 (ALL) SEM 细胞系移植的 NOD.CB17-Prkdcscid/J 小鼠中评估白藜芦醇作为预防剂防止 t(4;11)ALL 生长的功效。将 SEM 细胞注入尾静脉,并通过流式细胞术监测植入情况。一旦观察到植入,将白藜芦醇(10mg/kg 体重)溶于二甲基亚砜(DMSO)或单独的 DMSO(对照)中,每隔一天通过腹腔内注射,或每周 3 次注射长春新碱(0.5mg/kg 体重)共 4 周(每组 16 只)。血液中人类白血病细胞的百分比和生存曲线的比较表明,白藜芦醇不能抑制疾病的进展。对小鼠血清的液相色谱-串联质谱分析表明,白藜芦醇在注射后 1 小时迅速代谢为葡萄糖醛酸化和硫酸化形式,在 24-48 小时时,血清中几乎没有白藜芦醇或代谢物。这些数据表明,与体外模型的发现相反,肠胃外给予的白藜芦醇不具有作为预防高危 t(4;11)ALL 的潜在用途。