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海米定对胃癌的抗肿瘤作用及其机制

Anti-neoplastic efficacy of Haimiding on gastric carcinoma and its mechanisms.

作者信息

Ji Yu-Bin, Gao Shi-Yong, Ji Hong-Rui, Kong Qi, Zhang Xiu-Juan, Yang Bao-Feng

机构信息

Postdoctoral Research Station, Institute of Materia Medica, Harbin Commercial University, 138 Tongda Street, Daoli District, Harbin 150076, Heilongjiang Province, China.

出版信息

World J Gastroenterol. 2004 Feb 15;10(4):484-90. doi: 10.3748/wjg.v10.i4.484.

Abstract

AIM

To study the anti-neoplastic effect of Haimiding and its mechanisms of action.

METHODS

Experiments using MTT and colony formation were carried out to study the in vitro anti-neoplastic action of Haimiding, its in vivo anti-neoplastic action was studied by observing its effect on the weight of tumors in FC mice and S(180), H(22) tumor bearing mice, as well as their life spans. The effect of Haimiding on cell apoptosis and different stages of cell cycles in human gastric carcinoma cells were studied by flow cytometry. Its effect on Ca(2+) of human gastric carcinoma cells and the source of Ca(2+) during the change of Ca(2+) were observed by confocal laser scanning technique.

RESULTS

Haimiding showed a definite cytotoxicity to 8 human tumor cell lines, which was most prominent against BGC-823, E(ca-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 E(ca-109) tumor cells. It showed obvious inhibition on the growth of tumor in FC mice and S(180) bearing mice as well as prolonged the life span of H(22) bearing mice. It was able to induce apoptosis and elevate intracellular Ca(2+) concentration of tumor cells. The source of Ca(2+) came from both extracellular Ca(2+) influx and intracellular Ca(2+) release.

CONCLUSION

Haimiding is composed of a TCM preparation and 5-flurouracil. Its anti-neoplastic potency is highly enhanced by synergism as compared with either one of its components. Its mechanisms of anti-neoplastic action can be attributed to its action to initiate apoptosis of tumor cells by opening the membrane calcium channel and inducing intracellular Ca(2+) release to elevate Ca(2+) of the tumor cells.

摘要

目的

研究海嘧啶的抗肿瘤作用及其作用机制。

方法

采用MTT法和集落形成实验研究海嘧啶的体外抗肿瘤作用,通过观察其对FC小鼠及S(180)、H(22)荷瘤小鼠肿瘤重量及生存期的影响研究其体内抗肿瘤作用。采用流式细胞术研究海嘧啶对人胃癌细胞凋亡及细胞周期不同阶段的影响。采用共聚焦激光扫描技术观察海嘧啶对人胃癌细胞内[Ca(2+)]i的影响及[Ca(2+)]i变化时Ca(2+)的来源。

结果

海嘧啶对8种人肿瘤细胞株具有一定的细胞毒性,对BGC-823、E(ca-109)和HCT-8肿瘤细胞的毒性最为显著。对上述肿瘤细胞株的集落形成也有明显抑制作用,其中对E(ca-109)肿瘤细胞的抑制作用最为显著。对FC小鼠及S(180)荷瘤小鼠肿瘤生长有明显抑制作用,并延长H(22)荷瘤小鼠的生存期。能诱导肿瘤细胞凋亡并升高肿瘤细胞内[Ca(2+)]i浓度。Ca(2+)的来源既有细胞外Ca(2+)内流,也有细胞内Ca(2+)释放。

结论

海嘧啶由一种中药制剂与5-氟尿嘧啶组成。与单一成分相比,其抗肿瘤效力通过协同作用得到高度增强。其抗肿瘤作用机制可归因于通过打开膜钙通道并诱导细胞内Ca(2+)释放以升高肿瘤细胞内[Ca(2+)]i从而引发肿瘤细胞凋亡的作用。

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