| Purposes:To investigate the inhibitory effect of quercetin on transplantion tumor of breast cancer cell line MCF-7 in nude mice and its underlying mechanisms.Methods:MCF-7 cells were inoculated into the mammary fatty pad of nude mice to establish breast cancer model. Twenty-four BALB/c nude mice with xenograft tumors were randomized into four groups: group A (control), group B (quercetin), group C (5-fluorouracil,5-Fu), group D (quercetin+5-Fu). After treatment for 15 days, samples of breast cancer were collected to observe the inhibitory effect of medicines on the growth of tumor. The sections of tumors were observed under light microscope and electron microscope. Cell apoptosis in situ was examined by a TUNEL assay. Microvessel density (MVD) was estimated by FVIII-RA staining. Their expressions of Vascular endothelial growth factor (VEGF), Matrix Metalloproteinase-9 (MMP-9), Ki67 antigen and B-cell lymphoma/Leukemia-2(bcl-2) were detected by immunohistochemistry.Results: ①Quercetin could inhibit the growth of xenograft tumor: The weight of group A was significantly higher than that of group B, groupC and group D (P<0.05).The inhibition rates of tumor in group B, group C, group D were 36.46%,38.01%,48.52%,respectively. Inhibition rate of group D was higher than those of group B and group C, but there was no significant difference. ②Effect of quercetin on the toxic side effect of chemotherapy: Treatment with quercetin was no side effect. The toxic effect in combination group was significantly lower than that of 5-Fu group. At the end of this experiment, the weight of nude mice in group C decreased obviously than those of group A, group B and group D, with no difference between group A and group B. ③ lmmunohistochemical staining of Ki67 showed that the Ki67 label index (Ki67-LI )had significant difference between group A and group B,group C,group D (P<0.01),with no significant difference between group B,group C and group D, which indicated that quercetin could inhibit the proliferation of tumor cells. ④Detection of apoptosis in situ by a TUNEL assay showed that apoptosis index (AI) had significant difference between group A and group B, group C, group D(P<0.01),with significant difference between group D and group B,group C(P<0.05). AI/Ki67-LI rates had significant difference between group A and group B ,group C, group D(P<0.01),with significant difference between group D and group B, group C. These indicated that quercetin could induce apoptosis of tumor cell, and the effect increased with the combined application use of quercetin and 5-Fu. ⑤Immunohistochemical staining of bcl-2 showed significant difference between group A and group B, group C ,group D(P<0.05),which indicated that quercetin could inhibit the expression of bcl-2 in tumor cells. ⑥MVD estimation showed significant difference between group A and group B ,group C ,group D(P<0.01),with significant difference between group B ,group D and group C (P<0.05),which indicated that quercetin could reduce the MVD in breast cancer distinguishingly. ⑦Immunohistochemical staining of MMP-9 showed no significant difference between group A and group B ,group C ,group D (P<0.05),and the expression rate of MMP-9 was low in xenograft tumor of MCF-7 cells. ⑧Imumunohistochemical staining of VEGF showed significant difference between group A and group B,group C and group D(P<0.01),which indicated that quercetin could inhibit the expression of VEGF in breast cancer.Conclusions: Quercetin can inhibit the growth of transplantation tumor of breast cancer cell lines MCF-7 in nude mice ,and its mechanisms may beas follows: ①To inhihit the proliferation of tumor cells .②To induce the apoptosis of tumor cells by inhibiting the expression of bcl-2.③To inhibit the expression and activities of VEGF mainly, So that the angiogenesis in breast cancer is inhibited, retarding the tumor growth. Meanwhile,quercetin has no toxic effect on the body, and can alleviate the toxic side effect of tradi...
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