Abstract
Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Ascorbic Acid / pharmacology*
-
Blotting, Western
-
Carcinoma, Lewis Lung / drug therapy*
-
Carcinoma, Lewis Lung / pathology*
-
Cell Line
-
Cell Line, Tumor
-
Cell Proliferation
-
Cisplatin / pharmacology
-
Dose-Response Relationship, Drug
-
Lung Neoplasms / drug therapy*
-
Lung Neoplasms / pathology
-
Male
-
Matrix Metalloproteinase 2 / blood
-
Matrix Metalloproteinase 2 / genetics
-
Matrix Metalloproteinase 9 / blood
-
Matrix Metalloproteinase 9 / genetics
-
Mice
-
Mice, Inbred C57BL
-
Neoplasm Invasiveness
-
Plasminogen Activator Inhibitor 1 / genetics
-
Plasminogen Activator Inhibitor 1 / metabolism
-
Tissue Inhibitor of Metalloproteinase-1 / genetics
-
Tissue Inhibitor of Metalloproteinase-1 / metabolism
-
Tissue Inhibitor of Metalloproteinase-2 / genetics
-
Tissue Inhibitor of Metalloproteinase-2 / metabolism
-
Transplantation, Heterologous
-
Urokinase-Type Plasminogen Activator / blood
-
Urokinase-Type Plasminogen Activator / genetics
-
Vitamin K 3 / pharmacology*
Substances
-
Plasminogen Activator Inhibitor 1
-
Tissue Inhibitor of Metalloproteinase-1
-
Tissue Inhibitor of Metalloproteinase-2
-
Vitamin K 3
-
Urokinase-Type Plasminogen Activator
-
Matrix Metalloproteinase 2
-
Mmp2 protein, mouse
-
Matrix Metalloproteinase 9
-
Mmp9 protein, mouse
-
Ascorbic Acid
-
Cisplatin