Rapamycin in Growth Inhibition of Human Cervical Carcinoma HeLa Cell Subcutaneous Xenografts in Nude Mice and Its Mechanism

Objective To evaluate the inhibition effect of rapamycin (RAPA) on the growth of human cervical carcinoma subcutaneous xenografts in nude mice and its possible mechanism. Methods Nude mice were subcutaneously inoculated with HeLa cells to establish a subcutaneous transplantation tumor model of cervical cancer. Mice were randomly divided into 3 groups: control, low(1.5 mg/kg)and high dose (4.5 mg/kg) group. The nude mice were sacrifi ced 2 weeks after drug intervention, and the tumor volume and weight were observed during the therapeutic process. The mRNA and protein expressions of hypoxia-inducible factor-1alpha (HIF-1α), vascular endothelial growth factor (VEGF) and microvessel density(MVD)were detected by immunohistochemistry and RT-PCR. Results The carcinoma cell growth curve was significantly slow down after treated with Rapamycin. Compared with the control group, the average tumor volume and weight,VEGF protein levels,VEGF and HIF-1α mRNA levels, MVD were signifi cantly reduced in the low and high dose groups(P＜0.01),with no difference between different dose groups(P>0.05). Conclusion Rapamycin has obviously inhibition effect on Xenograft model in nude mice (volume weight), and the possible mechanism is to inhibit the expression of VEGF through inhibiting HIF-1α, thereby to inhibit the tumor angiogenesis.