General, Visceral and Transplant Surgery, Dept. of Surgery, Medical University of Graz, Austria.
Faculty of Medicine, Vilnius University, Lithuania.
Int J Biol Sci. 2019 Jun 4;15(8):1582-1590. doi: 10.7150/ijbs.35513. eCollection 2019.
Chemotherapy (CTx) with FOLFOX is indicated prior to resection of liver metastases; however, its effect is limited due to chemoresistance and its toxicity prevents from aggressive surgery needed in some cases. Hepatoprotective glycine has been shown to have anti-tumorigenic properties in various cancers. Thus, this study was designed to evaluate the effects of glycine combined with FOLFOX on colorectal liver metastases (CRLM). The effect of glycine combined with 5-fluorouracil and oxaliplatin was investigated on colorectal cancer (CC531). Further, Wag/Rij rats with CRLM were treated with 5% dietary glycine ± FOLFOX. µCT liver scan, anti-Ki67, and anti-CD31 were compared. Glycine alone and combined with CTx has no effect on both CC531 viability and tumor proliferation ; however, glycine significantly decreased tumor volume to about 42-35% of controls (p<0.05) with a 60% decreased tumor microvascular density (MVD) (p=0.004). Further glycine doesn't counteract anti-tumor properties of CTx. This study nicely demonstrates that glycine inhibits the growth of CRLM and does not decrease CTx effectiveness. Underlying mechanisms most likely include a decreased tumor MVD. Clinical trials are warranted to implement non-toxic hepatoprotective glycine in novel anti-cancer strategies in humans.
化疗（CTx）联合 FOLFOX 方案适用于肝转移灶切除术之前；然而，由于化疗耐药性，其疗效有限，并且其毒性会阻止某些情况下需要的激进手术。甘氨酸具有保护肝脏的作用，已被证明对多种癌症具有抗肿瘤特性。因此，本研究旨在评估甘氨酸联合 FOLFOX 对结直肠癌肝转移（CRLM）的影响。研究了甘氨酸联合 5-氟尿嘧啶和奥沙利铂对结直肠癌细胞（CC531）的影响。此外，用 5%饮食甘氨酸±FOLFOX 治疗 Wag/Rij 大鼠的 CRLM。比较了 µCT 肝脏扫描、抗 Ki67 和抗 CD31。甘氨酸单独和联合 CTx 对 CC531 的活力和肿瘤增殖均无影响；然而，甘氨酸显著降低肿瘤体积，约为对照组的 42-35%（p<0.05），肿瘤微血管密度（MVD）降低 60%（p=0.004）。此外，甘氨酸不会抵消 CTx 的抗肿瘤特性。这项研究很好地表明，甘氨酸抑制 CRLM 的生长，并且不会降低 CTx 的有效性。潜在的机制可能包括降低肿瘤 MVD。需要开展临床试验，将无毒的肝脏保护剂甘氨酸应用于人类新的抗癌策略中。
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