Study Of The Inhibitory Effect Of Quercetin On Transplantation Tumor Of Breast Carcinoma Cell Line MCF-7 In Nude Mice And Its Effect On The Cell Cycle

Objective: To study the inhibitory effect of quercetin on transplantation tumor of breast carcinoma cell line MCF-7 in nude mice and its effect on the cell cycle.Methods: The animal model of MCF-7 transplantation tumor in nude mice was constructed: 24 nude mice with transplantation tumor were randomized into 4 groups with six mice in each group. Group A: control group; Group B: quercetin group; Group C: adriamycin group; Group D: combining group (quercetin plus adriamycin). After 15 days of administration, the inhibitory effects of the drugs in each group were observed. The specimens were observed with light microscope and eletron microscope, analysed with flow cytometry, immunohistochemistry of Ki-67, cyclin D1 and p21WAF1/CIP1 gene protein product, in situ hybridization of p21WAF1/CIP1 and the number of nucleated bone marrow cells. Results: 1. The transplantation tumor weights of group A were significantly higher than those of group B,C and D (P<0.01). The inhibitory rates of group B,C and D were 36.46%,53.88% and 41.49%respectively, which indicated that quercetin had inhibitory effect on tumor. There was no significant difference among group B,C and D (P>0.05), indicating that the combining drugs had no synergistic effects.2. The results of immunohistochemical staining of Ki-67 showed that: Ki-67 label index of group A was the highest, group D was the second, both of them were higher than those of group B and C (P<0.01). There was no significant difference between group B and C, indicating that quercetin had inhibitory effect on cell proliferation, which could be enhanced by combining drugs. 3. Through flow cytometry analyzing, the rates of phase S on the whole cell cycle of group A were higher than those of group B,C and D (P<0.01), indicating that quercetin had inhibitory effect on tumor. The rates of phase G0/G1 on the whole cell cycle of group B,C and D were significantly lower than those of group A (P<0.01), which indicated that quercetin mainly acted on G1/S check point. There was no significant difference between group B and D (P>0.05), which indicated that combining drugs could not enhance the regulating effect of quercetin on the cell cycle.4. The immunohistochemical staining of cyclin D1 showed that: the expression level of cyclin D1 of group A was higher than those of group B,C and D (P<0.01), and there was no significant difference among group B,C and D (P>0.05), which indicated that quercetin could down-regulate the expression level of cyclin D1 and combining drugs could not enhance this effect.5. The immunohistochemical staining of p21WAF1/CIP1 showed that: the expression level of p21WAF1/CIP1 of group A and C was lower than group Band D (P<0.01), there was no significant difference between group A and C, between group B and D (P>0.05), which indicated that quercetin could up-regulate the expression level of p21WAF1/CIP1 protein and combining drugs could not enhance this effect.6. The in situ hybridization staining of p21WAF1/CIP1 showed that: the expression level of p21WAF1/CIP1 mRNA of group A and C were lower than group B and D (P<0.05). There was no significant difference between group A and C, between group B and D (P>0.05), indicating that quercetin could up-regulate p21WAF1/CIP1 gene, which could not be enhanced by combining drugs.7. The number of nucleated bone marrow cell (NNBMC) showed that: the NNBMC of group C was higher than group A,B and D (P<0.05), there was no significant difference among group A,B and D (P>0.05), which indicated that quercetin had no inhibitory effect on bone marrow and could antagonize the inhibitory effect of adriamycin on bone marrow.Conclusions: Quercetin has the inhibitory effect on transplantation tumor of breast carcinoma cell line MCF-7 in nude mice, its mechanisms may be related as follows: â‘ Inhibits the tumor cell proliferation.â‘¡Acts on G1/S check point, blocks the cell cycle in phase G1. â‘¢Down-regulates the level of cyclin D1 and inhibits the cell cycle progression. â‘£Up-regulates p21W...