六味地黄活血汤的抑瘤及促恶性表型逆转效应的初步研究

The Effect of Liu-We-Di-Huang Huo-Xue Tang on Antitumor and Reversion of Human tumor Cell Malignant Phenotypes

本研究初步证实了六味地黄活血汤(下简LHXT)对六株人肿瘤细胞均有明显抑瘤效应,IC_(50)均显著低于人胚肺细胞的IC_(50)。流式法(FCM)示该药使细胞聚集于G_2+M期,比对照高10倍。~3[H]-TdR掺入法则显示对DNA合成无抑制作用。软琼脂集落法证明该药对瘤细胞的抑制呈时间及剂量依赖性。免疫荧光法发现LHXT在抑制肿瘤细胞增殖同时,有明显促恶性表型逆转效应,对具高恶性、高转移率的PG细胞尤为突出。与阿霉素(ADM)促恶性表型逆转作用极其类似。该药并有明显抑制C-myc,及促P^(53)基因在PG细胞的扩增、表达。裸鼠荷瘤实验证实该药有明显抑瘤效应(P<0.05),与ADM同用效果更好(P<0.01),且显著优于单用ADM者(P<0.01)。

This study was carried out to investigate the effect of Liu-We-Di-Huang Huo-Xue Tang (LHXT) on antitumor and reversion of tumor cell malignant phenotypes. Compared with normal human lung fetal cells, the IC30 was showned that there was significant cytotoxicity effect on several human solid tumor cell lines by LHXT with MTT assay. The stomach adenocarcinoma cells,MGC-803 or BGC-823, giant carcinoma of the lung PG cells and the breast cancer cells BCaP37 were significant sensitivity to LHXT than that of the other cell lines. Result from PG cell counting indicated that the growth curves of LHXT inhibition effect were concentration and time dependent. There was no depressive effect on DAN synthetic. But the MGC-803 cells were gathered in G2+M phase by LHXT with FCM assay. By using immunofluoresceat atainning assay, the malignant phenotypes, microtuble, microfilament and microvilli of PG cells, MGC-803 cells and BCaP37 cell were reversed by LHXT dramatically. This reversive effect of PG cell was dominant. The results mentioned above was similar to that of Adriamycin. Besides, there was effect on reducing C-myc DNA amplication and expression and increase of P53 expression on PG cells by LHXT. The antitumor effect was also showed on nude mice loaded with BGC-823 cells significantly. Therefore, the LHXT not only may inhibite the human tumor cell proliferation in vitro and in vivo, but also may induce differentiation of cell morphology of tumor cell though its action on cytoskeletal structures. And it may influence the amplication and expression of some oncogenes or antioncogenes of human tumors.