海嘧啶体内外抗肿瘤作用研究

 目的研究海嘧啶抗胃癌作用及作用机制。方法采用MTT实验和集落形成实验观察海嘧啶的体外抗肿瘤作用;通过 海嘧啶对Fc小鼠和S₁₈₀,H₂₂荷瘤小鼠瘤重和生存时间的研究,观察海嘧啶的体内抗肿瘤作用。采用流式细胞仪测定海嘧啶对 人胃癌细胞凋亡及细胞周期的影响;采用激光扫描共聚焦技术观测海嘧啶对人胃癌细胞内Ca²⁺]_i的影响及Ca²⁺]_i变化时Ca²⁺的来源。结果 海嘧啶对8种人癌细胞具有一定的杀伤作用,其中以对BGC-823,Eca-109,HCT-8细胞的抑制作用最强;对 BGC-823,Eca-109,HCT-8细胞的集落形成有明显的抑制作用,并以对Eca-109细胞集落形成抑制作用最强;可明显抑制FC小鼠 和S₁₈₀小鼠瘤体的生长,明显延长H₂₂荷瘤小鼠的生存时间。海嘧啶可诱导肿瘤细胞凋亡,升高肿瘤细胞内Ca²⁺]_i的浓度, Ca²⁺]_i升高时Ca²⁺来源于细胞外钙内流和细胞内钙释放。结论海嘧啶有明显的抗肿瘤作用,其抗肿瘤机制为诱导肿瘤细 胞凋亡。海嘧啶通过开放细胞膜钙通道和引起细胞内钙释放两条途径升高肿瘤细胞内Ca²⁺]_i,启动细胞凋亡机制,从而诱导 肿瘤细胞凋亡。

Anti-neoplastic effect of Haimiding on gastric carcinoma and its mechanism

OBJECTIVE To study the anti-neoplastic effect of Haimiding and its mechanism.METHODS MTT and colony formation were used to study anti-neoplastic action of Haimiding in vitro. The anti-neoplastic action of Haimidiing in vivo was studied by observing its effect on the weight of tumors in FC mice and S180, H22 tumor bearing mice,as well as on the life spans of the mice. The effect of Haimiding on cell apoptosis and different stages of cell cycles in human gastric carcinoma cells was studied by flow cytometry. Its effects on Ca2 ]iof human gastric carcinoma cells and the source of Ca2 during the change of Ca2 ] i was observed by confocal laser scanning technique. RESULTS Haimiding showed a definite cytotoxicity to 8 human tumor cell lines, which was most prominent agaiast BGC-823, Eca-109 and HCT-8 tumor cells. It also exhibited an obvious inhibition on colony formation of the above tumor cell lines, which was most prominent in Eca-109 tumor cells. It showed obvious inhibition on the growth of tumor in FC mice and S180 bearing mice as well as prolonged the life span of H22 bearing mice. It was able to induce apoptosis and elevate intracellular Ca2 ]i concentration of tumor cells. The source of Ca2 came from both extracellular Ca2 influx and intracellular Ca2 release.CONCLUSION Haimiding has significant anti-tumour effect.Its mechanism of anti-neoplastic action could be attributed to its action of initiating the apoptosis of tumor cells by opening the membrane calcium channel and inducing intracellular Ca2 release to elevate Ca2 ]i of the tumor cells.