ABSTRACT
Objective:To investigate the effect of rapamycin on cell growth and migration of gallbladder cancer GBC-SD cells, and to discuss its potential in clinical therapy of gallbladder cancer. Methods: Proliferation of GBC-SD cells treated with different concentrations of rapamycin (12.5, 25, and 50 mmol/L) was examined by MTT assay. Cell cycle distribu-tion and apoptosis of GBC-SD cells treated with different concentrations of rapamycin were determined by flow cytometry. Migration ability of GBC-SD cells was assessed by Transwell assay. The expression of mTOR (mammalian target of rapam-ycin) and its phosphorylation in GBC-SD cells were examined by Western blotting assay. Results: Rapamycin significant-ly inhibited the phosphorylation of roTOR, but had no influence on the expression of roTOR in GBC-SD cells. Rapamycin significantly inhibited the growth of GBC-SD cells in a dose-dependent manner (P < 0.01). Raparnycin induced apoptosis of GBC-SD cells and arrested them at the G_1/S phase. Furthermore, rapamycin also significantly suppressed migration of GBC-SD cells as showed by Transwell assay (P < 0.01). Conclusion: Rapamycin can remarkably inhibit the growth and migration of gallbladder cancer cells, probably by inhibition of p-roTOR pathway, induction of apoptosis and cell cycle ar-rest of gallbladder cancer cells.
ABSTRACT
<p><b>OBJECTIVE</b>To study the effects of angiogenesis inhibitor endostatin on the growth and metastasis of gastric cancer in vivo.</p><p><b>METHODS</b>Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. Endostatin was administered sc at dose of 0 mg/kg, 2.5 mg/kg, 10.0 mg/kg and 20.0 mg/kg every other day for seven weeks. Eight weeks after implantation, the tumor size and inhibition rates and intratumoral microvessel density (MVD) and apoptotic index (AI) and the presence of metastasis are evaluated respectively after the mice were sacrificed.</p><p><b>RESULTS</b>Compared with the untreated controls, growth of the orthotopically implanted tumor was significantly reduced in size in mice treated with endostatin with an inhibition rate 0, 62.7%, 95.8% and 99.9% at the dosage of 0 mg/kg, 2.5 mg/kg, 10.0 mg/kg, and 20.0 mg/kg, respectively. The MVD was also decreased significantly in the treated mice [(13.7 +/- 3.90) versus (5.73 +/- 2.36), (2.17 +/- 1.28) and (0.66 +/- 0.25)]. The AI was increased significantly in the treated mice [(3.91 +/- 2.58)%, versus (6.76 +/- 5.03)%, (18.92 +/- 6.75)% and (28.57 +/- 10.34)%]. The incidences of peritoneal metastases was also significantly inhibited in the treated mice (87.1% versus 54.5%, 16.7% and 0). The incidences of liver metastases was also significantly inhibited in the treated mice (83.9% versus 27.3%, 8.3% and 0). The growth and metastasis of human gastric cancer implanted in nude mice were significantly inhibited in a dose-dependent manner (P < 0.05).</p><p><b>CONCLUSIONS</b>Angiogenesis inhibitor endostatin can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has strong inhibitory effect both on tumor growth and metastasis of human gastric cancer implanted in nude mice.</p>
Subject(s)
Animals , Humans , Male , Mice , Angiogenesis Inhibitors , Therapeutic Uses , Antineoplastic Agents , Therapeutic Uses , Apoptosis , Collagen , Therapeutic Uses , Endostatins , Mice, Inbred BALB C , Neoplasm Metastasis , Neoplasm Transplantation , Neovascularization, Pathologic , Peptide Fragments , Therapeutic Uses , Stomach Neoplasms , Drug Therapy , PathologyABSTRACT
Objective To investigate effects of CO_2 pneumoperitoneum,helium pneumoperitoneum,and laparotomy on(port-)site and visceral metastasis in BALB/c nude mice bearing human colon cancer xenografts.Methods A nude mouse model with human colon cancer LoVo cell line xenografts was used.The mice were randomly divided into four groups: CO_2 Pneumoperitoneum Group,Helium Pneumoperitoneum Group,Open Surgery Group,and Control Group.A biopsy was performed in the former 3 groups,and the Control Group received no surgical intervention. Results All the mice were sacrificed for pathological examinations.Orthotopic tumor xenograft was successfully established in all the mice of the four groups(100%,86/86).The rates of port-site metastasis were 9.5%(2/21) in the CO_2 Pneumoperitoneum Group,9.1%(2/22) in the Helium Pneumoperitoneum Group,and 19.0%(4/21) in the Open Surgery Group,respectively,without significant differences among the three groups(?~2=1.227,P=0.541).The rates of liver metastasis were 38.1%(8/21) in the CO_2 Pneumoperitoneum Group,31.8%(7/22) in the Helium Pneumoperitoneum Group,52.4%(11/21) in the Open Surgery Group,and 31.8%(7/22) in the Control Group,respectively,without significant differences among the four groups(?~2=2.543,P=0.468).Conclusions As compared with laparotomy and control groups,artificial pneumoperitoneum doesn't cause an increase of rates of port-site and visceral metastasis.Moreover,there is no significant difference between CO_2 pneumoperitoneum and helium pneumoperitoneum in rates of port-site and visceral metastasis.