Digestive Diseases and Sciences

, Volume 56, Issue 6, pp 1876–1883

Differential Effects of Vitamin K1 on AFP and DCP Levels in Patients with Unresectable HCC and in HCC Cell Lines

  • Brian I. Carr
  • Ziqiu Wang
  • Meifung Wang
  • Gang Wei
Original Article

DOI: 10.1007/s10620-010-1521-x

Cite this article as:
Carr, B.I., Wang, Z., Wang, M. et al. Dig Dis Sci (2011) 56: 1876. doi:10.1007/s10620-010-1521-x

Abstract

Purpose

DCP is a useful HCC tumor marker, which reflects a defect in vitamin K metabolism. We tested the hypothesis that vitamin K treatment of HCC patients might suppress this marker and possibly AFP also.

Experimental Design

HCC patients who had both elevated AFP and DCP were included. A phase I cohort was treated with escalating vitamin K1 intravenous weekly doses and a 27-patient phase II cohort was then treated with a fixed oral daily dose.

Results

A maximum tolerated dose was not reached up to 100-fold the normal vitamin K1 dose. No toxicities were found up to 1,000 mg/infusion. In the phase II cohort, 93% of patients had tumor marker responses by decreased DCP levels, but only 22% had responses by decreased AFP levels. CT scans showed 11% of patients had PRs, 59% had stable tumors and 29.6% had tumor progression. Mechanism studies showed that vitamin K1 induced phosphorylation of JNK and c-Jun and caspase-mediated apoptosis.

Conclusions

Vitamin K1 was non-toxic at high doses, strongly inhibited plasma DCP levels, but weakly suppressed AFP levels. The results provide evidence that the two tumor markers are not directly linked and that DCP levels may not reflect HCC cell growth, as DCP levels were decreased in patients without AFP change, and were suppressed in vitro at 1% of the vitamin K1 concentration needed to inhibit AFP.

Keywords

AFP DCP HCC Responses Vitamin K 

Abbreviations

ECOG

Eastern Cooperative Oncology Group

AFP

Alfa-fetoprotein

DCP

Des-gamma carboxy prothrombin

HCC

Hepatocellular carcinoma

CT

Computed axial tomography scan

JNK

Jun kinase

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Brian I. Carr
    • 1
    • 2
    • 3
  • Ziqiu Wang
    • 1
  • Meifung Wang
    • 1
  • Gang Wei
    • 1
  1. 1.Department of Medical Oncology, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Liver Tumor Program, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  3. 3.Department of Nutrition and Experimantal BiologySaverio De Bellis Medical Research Institute70013Italy