Cancer metastasis is the leading cause of death in
cancer patients. However, it is unclear whether
lycopene can act as an adjuvant to increase the anti-metastatic activity of anticancer drugs. Here, we examined the anti-lung-metastatic effects and the mechanism of
lycopene in combination with
sorafenib in C57BL/6 mice xenografted with
Lewis lung carcinoma (LLC) cells. The mice were divided into five groups: (1)
tumor control; (2)
lycopene (5 mg/kg); (3)
sorafenib (30 mg/kg); (4)
lycopene (2 mg/kg) +
sorafenib (30 mg/kg); (5)
lycopene (5 mg/kg) +
sorafenib (30 mg/kg). The results showed that
lycopene reduced the number of metastatic
tumors in the lungs, which was further suppressed by the combined treatment with
sorafenib. The activities of
matrix metalloproteinase (MMP)-2 and-9 were further inhibited and
TIMP-1 and-2, and NM23-H1, the
MMPs negative modulators, were further activated in the combined treatment. Mechanistically, we found that
lycopene and
sorafenib could additively inhibit the
mitogen-activated protein kinase (MAPK) pathways, as shown by the
protein phosphorylation of ERK1/2, JNK1/2 and p38 were reduced additively. Overall, the present study demonstrates that
lycopene in combination with
sorafenib additively inhibits the lung
metastasis of
tumor, indicating
lycopene has potential as an adjuvant for
sorafenib in
cancer treatment.