This paper discussed the synergistic anti-
tumor effect of
Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human
liver cancer cell line Huh-7 and
tumor bearing mice. The effects of
Shuangdan Capsules combined with
5-FU on the activity and
vascular endothelial growth factor(
VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of
drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-
tumor effect of
drug combination and the distribution of
tumor blood flow in
tumor bearing mice by using molecular imaging. HPLC analysis showed that
Shuangdan Capsules mainly consisted of danshensusodium,
protocatechuic aldehyde,
paeoniflorin,
rosmarinic acid, alkannic
acid,
salvianolic acid B, and
paeonol. In MTT experiment, the inhibition rate of
Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 μmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-
hepatoma cells effect. The expression of
VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo,
Shuangdan Capsules combined with
5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted
tumor nude mice; serum expression of CD31 and
VEGF in nude mice were decreased, while
caspase-3 was increased. Meanwhile, the
drug combination significantly inhibited the expressions of MMP2 and
VEGF in
tumor tissues. Ultrasound showed that
Shuangdan Capsules combined with
5-FU also inhibited
tumor angiogenesis and reduced blood flow of
tumor tissue. The results showed that
Shuangdan Capsules combined with
5-FU may inhibit
tumor angiogenesis by inhibiting
VEGF and MMP2 expressions, thereby blocking
tumor growth.