Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.
Department of Biostatistics, University of Michigan Health System, Ann Arbor, Michigan.
Cancer. 2016 Mar 1;122(5):722-9. doi: 10.1002/cncr.29793. Epub 2015 Nov 30.
Resveratrol inhibits the growth of ovarian carcinoma cells in vitro through the inhibition of glucose metabolism and the induction of both autophagy and apoptosis. In the current study, we investigated the metabolic and therapeutic effects of resveratrol in vivo.
A fluorescent xenograft mouse model of ovarian cancer was used. Mice were treated with cisplatin, resveratrol, or vehicle alone. Tumor burden was assessed using whole-body imaging. The effect of resveratrol on glucose uptake in vivo was determined using micro-positron emission tomography scanning. To determine whether resveratrol could inhibit tumor regrowth, tumor-bearing mice were treated with cisplatin followed by either daily resveratrol or vehicle. Autophagic response in resected tumors taken from mice treated with resveratrol was examined by transmission electron microscopy. Glycolysis and mitochondrial respiration in ovarian tumor cells after treatment with resveratrol was assessed.
Mice treated with resveratrol and cisplatin were found to have a significantly reduced tumor burden compared with control animals (P<.001). Resveratrol-treated mice demonstrated a marked decrease in tumor uptake of glucose compared with controls. After treatment with cisplatin, "maintenance" resveratrol resulted in the suppression of tumor regrowth compared with mice receiving vehicle alone (P<.01). Tumors resected from mice treated with resveratrol exhibited autophagosomes consistent with the induction of autophagy. Treatment with resveratrol inhibited glycolytic response in ovarian tumor cells with high baseline glycolytic rates.
Treatment with resveratrol inhibits glucose uptake and has a significant antineoplastic effect in a preclinical mouse model of ovarian cancer. Resveratrol treatment suppresses tumor regrowth after therapy with cisplatin, suggesting that this agent has the potential to prolong disease-free survival. Cancer 2016;122:722-729. © 2015 American Cancer Society.
白藜芦醇通过抑制葡萄糖代谢和诱导自噬和凋亡，抑制体外卵巢癌细胞的生长。在本研究中，我们研究了白藜芦醇在体内的代谢和治疗作用。
使用荧光异种移植卵巢癌小鼠模型。用顺铂、白藜芦醇或单独载体处理小鼠。使用全身成像评估肿瘤负担。使用微正电子发射断层扫描确定白藜芦醇对体内葡萄糖摄取的影响。为了确定白藜芦醇是否能抑制肿瘤复发，用顺铂处理荷瘤小鼠，然后用白藜芦醇或载体进行每日治疗。通过透射电子显微镜检查从用白藜芦醇治疗的小鼠中取出的肿瘤中自噬反应。评估经白藜芦醇处理后的卵巢肿瘤细胞中的糖酵解和线粒体呼吸。
与对照动物相比，用白藜芦醇和顺铂治疗的小鼠肿瘤负担明显降低（P<.001）。与对照组相比，白藜芦醇治疗的小鼠肿瘤摄取葡萄糖的量明显减少。用顺铂治疗后，与单独接受载体的小鼠相比，“维持”白藜芦醇治疗导致肿瘤生长抑制（P<.01）。从用白藜芦醇治疗的小鼠中切除的肿瘤显示出与自噬诱导一致的自噬体。用白藜芦醇治疗抑制了具有高基线糖酵解率的卵巢肿瘤细胞的糖酵解反应。
白藜芦醇治疗可抑制葡萄糖摄取，并在卵巢癌的临床前小鼠模型中具有显著的抗肿瘤作用。白藜芦醇治疗抑制顺铂治疗后的肿瘤复发，表明该药物有可能延长无病生存期。癌症 2016;122:722-729。©2015 美国癌症协会。
