Inhibitory Effect Of Rapamycin On Tumor Growth In Nude Mice Bearing Subcutaneous Xenograft Human Cervical Carcinoma

Objective: To explore the inhibiting effect of rapamycin on the growth of human cervical carcinoma cells in nude mice and on the expression of HIF-1αand VEGF. The correlation between HIF-1αand VEGF was studied. This may provide theory basis to the anti-tumor treatment of cervical cancer through rapamycin blocking up the expression of HIF-1αand VEGF.Methods: Tumors were established by injection of 1×10~8 tumor cell named Hela into the right armpit of nude mice. When the inoculation car- cinoma grows to 8 millimeter the mice were classified randomly into three groups: control, low dose group(1.5mg/kg), High dose group(4.5mg/kg). Inje- ction dose was 200ug once, which was carried out for fourteen times (one time each day). Effects of grows suppression were observed though the volume and the average weight of neoplasia; the expression of HIF-1αand VEGF was examined through immunohistochemical stain and RT-PCR. The data was assayed using SPSS11.5 soft ware.Result:1.The tumor volume was 984.094±323.635mm3, 396.513±163.959mm3, 315.112±137.807mm3 in control, Rapamycin low dose group and Rapamy- cin high dose group respectively. while, the tumor weight was 0.633±0.194g, 0.307±0.112g, 0.206±0.053g Correspondingly. The carcinoma cell growth curve was significantly lower after treated with Ra- pamycin. The average volume and the average weight of neoplasia significantly decreased in Rapamy- cin group compared with control(P<0.05).2.Immunohistochemical stain indicated that, VEGF expression was downregulated in Rapamycin low dose group and Rapamycin high dose group compared with control(P<0.05); but there were not diffrences between Rapamycin low dose group and Rapamycin high dose group(P>0.05).3.RT-PCR indicated that, HIF-1αand VEGF expression was downer- gulated in Rapamycin low dose group and Rapamycin high dose group compared with control(P<0.05); but there were not diffrences between Rapamycin low dose group and Rapamycin high dose group(P>0.05).Conclusion: Rapamycin have obviously inhibiting effect on inocula- tion carcinoma, and the mechanism is to inhibite the expression of VEGF through inhibiting HIF-1α. As a result, the formation of tumor vessel was inhibited and the tumor apoptosis was induced.