The inhibitory effect of C225 alone or in combination with DDP on the growth of transplanted human cervical cancer in nude mice.

Objective:To explore the mechanism by which C225 alone or combined with DDP inhibited the growth of transplanted human cervical cancer HeLa cells in nude mice. Methods:Forty nude mice bearing human cervical cancer HeLa cells were randomly divided into 4 groups:the control group,C225 group,DDP group,and C225+DDP group,with 10 mice in each group. The four groups of nude mice were injected 0.9% normal saline (NS),C225 (1 mg/mouse),DDP (5 mg/kg),and C225 + DDP (C225 1 mg/mouse +DDP 5 mg/kg),respectively,twice per week for four weeks. At the end of the experiment,the tumor was removed and the volume and weight of tumor were measured. The tumor inhibition rate was calculated. The morphological changes of tumor cells were observed by optical microscopy and electron microscopy. The expressions of p27Kip1 and cyclin D1 in the transplanted tumor were detected by immunohistochemistry. Results:The tumor inhibition rates were 37.14%,46.96%,and 69.32% for C225 group,DDP group,and C225 + DDP group. Microscopy showed that HeLa cells had a marked proliferation and a high cellular atypia in the control group. But the tumor cells in the treatment group were significantly decreased and the stromal cells were markedly increased. A great amount of cell necrosis was observed in the DDP group and the C225+DDP group,especially in the C225+DDP group. Immunohistochemistry showed that the expression levels of p27Kip1 in the C225 group and C225+DDP group were significantly increased compared with the control group (P0.01,P0.05). There was no significant difference in p27Kip1 expression between the DDP group and the control group. The expression level of cyclin D1 was lower in the C225 group and C225+DDP group than that in the control group (P0.05,P0.01),but the difference between the DDP group and the control group was not significant (P0.05). Conclusion:C225 affected the growth of transplanted cervical cancer in nude mice by upregulating the expression of p27Kip1 and inhibiting the expression of cyclin D1. The tumor inhibition rate of C225+DDP was higher than that induced by C225 alone. It may be related with the increased sensitivity of HeLa cells to DDP by C225.