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| 1 | Inhibitory effect of topiramate on Lewis lung carcinoma metastasis and its relation with AQP1 water channel显示文摘AIM: To study the effect of topiramate on tumor metastasis and its relation with aquaporin 1 (AQP1) water channel. METHODS: Lewis lung carcinoma metastatic model was used to determine the effect of topiramate on tumor growth and metastasis. Colorimetric estimation was used to investigate the action of topiramate on carbonic anhydrase (CA) activity. Western blotting and immunohistochemical analysis were used to study the influence of topiramate on AQP1 water channel expression in lungs or tumor tissues of mice bearing Lewis lung carcinoma.RESULTS: Treatment with topiramate (120 mg.kg^-1.d^-1, ig for 20 d) reduced the growth of primary tumor signifi-cantly (P<0.05). Its inhibitory rate of metastasis was 81.25 %. Topiramate inhibited CA activity in lungs of mice in a dose-dependent manner. Topiramate apparently decreased AQP1 protein expression and immunostaining in lungs or in tumor microvessel endothelial cells of mice. CONCLUSION: Suppression of AQP1 water channel expression may be an important pathway for the inhibitory effect of topiramate on tumor metastasis. | BingMA YangXIANG TaoLI He-mingYU Xue-junLI | 2004 | Acta Pharmacologica Sinica2004，25，1： | 25 |
| 2 | Acetazolamide inhibits aquaporin-1 protein expression and angiogenesis显示文摘AIM: To study effects of acetazolamide on aquaporin-1 (AQP1) protein expression and angiogenesis. METHODS: Establishing Lewis-lung-carcinoma model, the localization of AQP1 in tumor tissues was investigated by immuno- histochemical methods; The biological activity of acetazolamide was detected by endothelial cells proliferation test (MTT) assay and chorioallantoic membrane (CAM) vascular inhibition test. RESULTS: Immunohistochemical localization of AQP1in mice tumor was labeled in capillaries, post capillary venules endothelial cells. After being treated with acetazolamide, the number of capillaries and post capillary venules was significantly decreased in tumor tissue. Acetazolamide showed significant inhibitory effect on angiogenesis in CAMand endothelial cell proliferation. CONCLUSION: Acetazolamide might be identified and developed as one of potential lead compounds for a new therapeutic intervention in inhibiting cancer angiogenesis. | YangXIANG BingMA TaoLI Jun-weiGAO He-mingYU Xue-junLI | 2004 | Acta Pharmacologica Sinica2004，25，6： | 23 |
| 3 | Effects of acetazolamide and anordiol on osmotic water permeability in AQP1-cRNA injected Xenopus oocyte显示文摘AIM: To study the effects of acetazolamide and anordiol on osmotic water permeability in aquaporin 1 (AQP1)-cRNA injected Xenopus oocyte and their mechanisms. METHODS: AQP1 gene constructed in pBluescript was transcripted into cRNA in vitro and then the cRNA was injected in Xenopus oocytes. The effects of acetazolamide and anordiol on the water transport function of AQP1 were observed by assaying the osmotic swelling of oocytes.In addition, their effects on protein expression of AQP1 were quantitatively investigated by Western blotting method.RESULTS: After incubation for 15 min or 72 h, acetazolamide, a carbonic anhydrase inhibitor, equally reduced the water permeability of AQPI-cRNA injected oocyte in a dose-dependent manner. After incubation for 72 h, anordiol,an antiestrogen with partial estrogenic activity, reduced the osmotic water permeability dose dependently as well;however, no discernable action was observed after incubation with anordiol for 15 min. The Western blotting analysis showed that acetazolamide did not influence the protein expression of AQP1. However, after incubation for 72 h with anordiol (10 μmol/L), the quantity of AQP1 in the oocyte membrane was decreased dramatically(P<0.05). CONCLUSION: Both acetazolamide and anordiol inhibited the osmotic water permeability of AQP1-cRNA injected oocyte, but their mechanisms were different. Acetazolamide functionally inhibited the osmotic water permeability of AQP1, whereas anordiol primarily decreased the amount of AQP1 protein in the oocyte membrane. | BingMA YangXIANG Sheng-meiMU TaoLI He-mingYU Xue-junLI | 2004 | Acta Pharmacologica Sinica2004，25，1： | 6 |
| 4 | Proteomics: a new approach for drug discovery显示文摘Proteomics is a bridge that crosses genome to drug discovery. Proteomic studies will provide possible targets for therapeutic usage and moreover increase the efficiency of the downstream of drug discovery process. By using the 2-D electrophoresis combining with MS technology, which is most preva-lent techniques of proteome, we have identified more than | Xue-junLI YangXIANG Hui-kaiTIAN BingMA Xiao-haoYAO Hong-meiZHANG He-mingYU | 2004 | Acta Pharmacologica Sinica2004，25，11： | 0 |
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