Unconjugated Bilirubin Inhibits Metastasis in NPC

In this study, we investigated the prognostic value of unconjugated bilirubin (UCB), which was previously considered a byproduct of heme catabolism, in NPC patients and examined the effects of UCB on NPC metastasis. The receiver operating characteristic analysis–generated UCB cutoff point for DMFS was 9.7 μmol/L. We found that higher UCB levels were significantly associated with favorable distant metastasis-free survival (DMFS, 93.3% vs. 84.2%, P < 0.001) in NPC patients and was an independent predictor for DMFS (HR, 0.416; 95% confidence interval, 0.280–0.618; P < 0.001). We next found that UCB treatment impaired the invasion capability of NPC cells and potently inhibited lung metastasis of NPC cells in nude mice. Further investigation showed that UCB inhibited reactive oxygen species production, which is involved in the repression of ERK1/2 activation and matrix metalloproteinase-2 (MMP-2) expression. Moreover, lower levels of ERK1/2 phosphorylation and MMP-2 expression were observed in the NPC lung metastases of nude mice administered UCB. Taken together, our results indicate that UCB is a significantly favorable factor for DMFS in NPC patients and may play an important role in NPC chemoprevention. Cancer Prev Res; 9(2); 180–8. ©2015 AACR.

Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Deng, C.-C., Xu, M., Li, J., Luo, X.-L., Zhu, Y.-J., Jiang, R., Zhang, M.-X., Lei, J.-J., Lian, Y.-F., Zou, X., You, R., Chen, L.-Z., Feng, Q.-S., Bei, J.-X., Chen, M.-Y., Zeng, Y.-X. Tags: Research Articles Source Type: research