Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice

AIM: To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2 and bax.METHODS: A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneou...

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Published in:World journal of gastroenterology : WJG 2005-01, Vol.11 (2), p.280-284
Main Authors: Zhou, Hai-Bo, Chen, Juan-Juan, Wang, Wen-Xia, Cai, Jian-Ting, Du, Qin
Format: Article
Language:English
Subjects:
Angiogenesis Inhibitors - therapeutic use
Animals
Apoptosis - drug effects
bcl-2-Associated X Protein
Brief Reports
Cell Division - drug effects
DNA Primers
Humans
Mice
Mice, Nude
Proto-Oncogene Proteins c-bcl-2 - genetics
Resveratrol
Reverse Transcriptase Polymerase Chain Reaction
Stilbenes - therapeutic use
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Transplantation, Heterologous
初级胃癌细胞
抗癌活性
消化系统
灌注治疗
白藜芦醇
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Summary:AIM: To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2 and bax.METHODS: A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. Resveratrol (500mg/kg, 1000mg/kg and 1500mg/kg) was directly injected beside tumor body 6 times at an interval of 2d. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alterations by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis-regulated genes bc/-2and baxby immunohistochemical staining and PT-PCR.RESULTS: Resveratrol could significantly inhibit carcinoma growth when it was injected near the carcinoma. An inhibitory effect was observed in all therapeutic groups and the inhibition rate of resveratrol at the dose of 500mg/kg, 1000 mg/kg and 1500mg/kg was 10.58%, 29.68% and 39.14%, respectively. Resveratrol induced implanted tumor cells to undergo apoptosis with apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation. The inhibition rate of 0.2mL of normal saline solution, 1500mg/kg DMSO, 500mg/kg resveratrol, 1000mg/kg resveratrol, and 1500mg/kg resveratrol was 13.68±0.37%, 13.8±0.43%, 48.7±1.07%, 56.44±1.39% and 67±0.96%, respectively. The positive rate of bcl-2 protein of each group was 29.48±0.51%, 27.56±1.40%,11.86±0.97%, 5.7±0.84% and 3.92±0.85%, respectively by immunohistochemical staining. The positive rate of bax protein of each group was 19.34+0.35%, 20.88±0.91%, 40.02±1.20%, 45.72±0.88% and 52.3± 1.54%, respectively by immunohistochemical staining. The density of bcl-2 mRNA in 0.2mL normal saline solution, 1500mg/kg DMSO, 500mg/kg resveratrol, 1000mg/kg resveratrol, and 1500mg/kg resveratrol decreased progressively and the density of bax mRNA in 0.2mL normal saline solution, 1500mg/kg DMSO, 500mg/kg resveratrol, 1000mg/kg resveratrol, and 1500mg/kg increased progressively with elongation of time by RT-PCR.CONCLUSION: Resveratrol is able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated by down-regulating apoptosis-regulated gene bcl-2 and up-regulating the expression of apoptosis-regulated gene bax.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v11.i2.280