OBJECTIVE To study the inhibitory effect and mechanism of total
flavonoids from
Melicope pteleifolia (TF-MPL) on transplanted
tumor of
colorectal cancer in
nude mice.
METHODS The transplanted
tumor model of
colorectal cancer was induced by injecting 0.2 mL
colorectal cancer cell LoVo subcutaneously via the right
armpit of
nude mice. After successful modeling,
nude mice were randomly divided into model group,
5-fluorouracil group (positive control, 10 mg/kg), TF-MPL high-
dose and low-
dose groups (25, 12.5 mg/kg); a normal group (
normal saline containing 0.3%
carboxymethyl cellulose sodium) without modeling was additionally set up, with 6
mice in each group. Each group was intraperitoneally injected with the corresponding
drug solution/
solvent for 21 consecutive days. The inhibitory rate of the transplanted
tumor,
liver and
spleen index, and the levels of
tumor necrosis factor-α (TNF-α) and
interleukin-6 (
IL-6) in
serum were detected after the last medication; the morphological changes of
tumor tissue were observed; immunohistochemical
staining was used to detect
protein expressions of Toll- like receptor 4 (TLR4) and nuclear factor-κB subunit p65 (NF-κB p65) in
tumor tissue of
nude mice.
Western blot assay was used to detect
protein expressions of TLR4,
myeloid differentiation factor 88 (MyD88),
TNF receptor-associated factor 6 (
TRAF6),
interleukin-1 receptor-associated kinase 1 (IRAK-1), NF-κB p65 and
caspase-3 in
tumor tissue of
nude mice. RESULTS Compared with the model group, TF-MPL high-
dose group showed a significant decrease in
tumor weight (inhibitory rate of 36.91%),
liver and
spleen index,
serum levels of TNF-α and
IL-6 and
protein expressions of TLR4, MyD88,
TRAF6,IRAK-1 and NF- κB p65 (P<0.05 or P<0.01); the expression of
caspase-3 protein was increased significantly (P<0.05), and more
tumor cell shrinkage and deformation, nuclear pyknosis and fragmentation were observed. CONCLUSIONS TF-MPL can significantly inhibit the
growth of transplanted
tumor of
colorectal cancer in
nude mice, the mechanism of which may be associated with reducing inflammatory response, inhibiting TLR4/MyD88/NF-κB signaling pathway, and promoting
apoptosis in
colorectal cancer cells.