Rationale:
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). Methods: The effect of
glycine combined with
5-fluorouracil and
oxaliplatin was investigated in vitro 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. Results:
Glycine alone and combined with CTx has no effect on both CC531 viability in vitro and
tumor proliferation in vivo; however,
glycine significantly decreased
tumor volume to about 42-35% of controls in vivo (p<0.05) with a 60% decreased
tumor microvascular density (MVD) (p=0.004). Further
glycine doesn't counteract anti-
tumor properties of CTx. Conclusions: 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.