|
The application can increase tumor recurrence or neoplastic traditional immunosuppressants after organ transplantation, organ transplant surgery is very successful, this may also be the cause of death in patients. New immunosuppressant rapamycin not only with hepatic, renal toxicity, and good patient tolerance, also has recently reported to inhibit a variety of tumor growth and metastasis, including colon cancer, kidney cancer, pancreatic cancer, breast cancer. The study confirmed the anti-tumor mechanism of rapamycin may inhibit tumor cell proliferation and induce apoptosis of tumor cells; inhibit tumor angiogenesis, and so on, but the exact mechanism is unclear. \In recent years, domestic and foreign research confirmed that rapamycin can inhibit liver cancer cell proliferation and induce apoptosis of hepatoma cells to inhibit tumor growth, generated through the inhibition of liver tumor vascular As to whether rapamycin can inhibit liver cancer growth and metastasis domestic, outside fresh have been reported. Objective To investigate the rapamycin neomycin produced inhibition of liver cancer tumor vascular and related mechanisms, simultaneous detection of the inhibition of the growth of liver cancer. Method in vivo experiments, the establishment of human hepatocellular carcinoma transplanted into nude mice model, rapamycin were randomly divided into conventional dose group (1.5 mg / kg / d), low-dose group (0.15 mg / kg / d), the high-dose group (4.5 mg / kg / d) and the control group, intraperitoneal injection, the control group was given the same volume of saline. Eyeball phlebotomy animals were sacrificed three weeks after treatment, specimens from serum samples, enzyme-linked immunosorbent assay (ELISA) to detect the level of expression of vascular endothelial growth factor (VEGF); the experiment, recorded every three days subcutaneous tumor size and observe animals in general status, tumor growth curve; subcutaneous tumor after the end of the experiment, carefully peel vernier caliper measurement of tumor size, tumor weight and weight mice weighing paraffin-embedded routine biopsy specimens of CD34 marker of endothelial cell line tumor microvessels (MVD) count; open the abdominal cavity and chest, careful observation of the presence or absence of metastatic nodules specimens from the animals liver and lungs, through general observation and biopsy detection of tumor metastasis. In vitro, primary cultured human umbilical vein endothelial cell migration assay by MTT assay, flow cytometry rapamycin on VEGF-induced vascular endothelial cell proliferation, migration, cell cycle and apoptosis. Results in the in vivo experiments, the rapamycin conventional dose group nude mice tumor growth was inhibited significantly reduced tumor MVD drop Serum VEGF levels significantly decreased (142.35 ± 53.64 vs 259.21 ± 82.68,17.09 ± 2.34 vs 25.77 ± 2.49, 66.84 ± 6.90 vs 78.78 ± 3.63) (P lt; 0.05). Compared with the control group, the low-dose group, the high-dose group, tumor volume, MVD and serum VEGF levels, although subject to some degree of inhibition, but not statistically significant. Meanwhile, in the above each group of animals were not observed to liver cancer metastases. Vitro experiments, rapamycin inhibition of VEGF-induced HUVECs proliferation and migration, flow cytometry confirmed HUVECs detained in the G0/G1 phase, increased rate of apoptosis. Conclusions (1) rapamycin can be generated through the inhibition of liver tumor vascular play the anti-tumor effect. (2) The anti-angiogenic rapamycin may inhibit vascular endothelial cell proliferation, migration, and induce endothelial cell apoptosis. (3) the anti-tumor effect of rapamycin has guiding significance not only for the choice of immunosuppressant after liver transplantation may also be used as a prevention and treatment of tumor proliferation, recurrence and metastasis of drugs used clinically.
|