|
Objective: To study rapamycin on human cervical cancer Hela transplanted into nude mice in vivo growth. By observing the hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression, and to further explore whether inhibition of VEGF expression by inhibiting the expression of HIF-1α, and ultimately effective inhibition of cervical cancer bare mouse xenograft tumor growth, rapamycin provide a theoretical basis for anti-cancer therapy for cervical cancer. Method: the nude mouse model of cervical carcinoma Hela prepared to a concentration of 1 × 108/ml cell suspension, planted in 15 4 to 6-week-old nude mice right axillary subcutaneous until the tumor grew to a diameter of up to 0.8cm (about 15 days), 15 nude mice were randomly divided into 3 groups (n = 5): control group, rapamycin low dose group (1.5mg/kg), rapamycin the neomycin high dose group (4.5mg/kg). Respectively, to the volume of the solution 0.2ml, administered by intraperitoneal injection once a day, for 14 days. After injection, observed daily for tumor survival state, every 2 days, the longest diameter of the tumor were measured with a vernier caliper (a) and shortest diameter (b), to calculate the tumor volume (V, V = 1/6πab2), and draw a subcutaneous tumor growth curve. After 14 days of treatment the mice were sacrificed, determination of the weight and size of the tumor, and calculate the rate of tumor suppressor application of immunohistochemistry and RT-PCR detected by planting tumor VEGF and HIF-1α change. Statistical analysis of the resulting data applications SPSS11.5 system package for processing. Results: 1 control group, rapamycin low-dose group, the average tumor volume of rapamycin in the high dose group were 984.094 ± 323.635mm3, 396.513 ± 163.959mm3, 315.112 ± 137.807mm3; mean tumor weight were 0.633 ± 0.194 g, 0.307 ± 0.112g, 0.206 ± 0.053g. Compared with the control group, rapamycin low dose group and high dose group, tumor growth curves slowing volume inhibition rates were 59.7%, 68.0% (P lt; 0.05); tumor weight inhibition rates were 51.5%, 67.5% (P lt; 0.05). Immunohistochemical detection: Compared with the control group, rapamycin low dose group and high dose groups of VEGF protein content was significantly lower (P lt; 0.05), but the low-dose group and high dose group had no significant difference (P gt; 0.05). Detection 3.RT-PCR: compared with the control group, rapamycin in the low-dose group and high dose groups of VEGF and the HIF-1αmRNA content was significantly lower (P lt; 0.05), but the low-dose group and high dose group, no significant differences (P gt; 0.05). Conclusion: Rapamycin in experimental animals tumor-bearing growth (size, weight) significantly inhibited the mechanism by inhibiting the expression of HIF-1α, thereby inhibiting the synthesis of VEGF in tumor angiogenesis was inhibited.
|