毛喉萜抑制人胃癌细胞BGC－823增殖与ras基因表达相关性研究

Relationship between Expression of Ha-ras and Inhibition of Proliferation by Forskolin in Human Gastric Cancer Cell Line BGC-823

毛喉萜（ｆｏｒｓｋｏｌｉｎ）对人胄癌细胞ＢＧＣ－８２３增殖有明显抑制作用，具药物剂量和作用时间之依赖性。剂量为２×１０^（－５）ｍｏｌ／Ｌ之毛喉萜使胃癌细胞在软琼脂中形成集落的能力显著降低；癌基因ｃ－Ｈａ－ｒａｓ之表达明显被抑制，细胞核中与ｒａｓ基因上游调控区２．５ｋｂ片段结合的三种蛋白结合能力下降。联系到以同样浓度药物处理胃癌细胞７２ｈ，细胞质、膜与细胞核中蛋白激酶Ｃ（ＰＫＣ）活性均下降的现象，可能ＰＫＣ活性下降与Ｈａ－ｒａｓ基因上游片段２．５ｋｂ结合蛋白之结合能力下降存在相关性，ＰＫＣ可能通过影响ＤＮＡ结合蛋白的磷酸化作用，导致了Ｈａ－ｒａｓ基因表达之被阻抑。而ｒａｓ基因表达下降可能是毛喉萜抑制胃癌细胞增殖的一个重要分子事件。

The proliferation of human gastric cancer cell line BGC-823 is inhibited obcviously by diterpene forskolin. The inhibition depends upon the dose of the medicine and the treated time.After treatment with forskolin,the foci formation in soft agar is decreased markedly. The expression of oncogene Ha-ras and the binding ability of nuclear proteins (53 kD, 35 kD, 26 kD) which bind to the 2. 5 kb fragment of ras upstream region are decreased simultaneously when cells are treated by forskolin (2×10-5M) for 72 hrs. At the same time, the PKC activities of cytosol,membrane and nucleus are decreased. So it seems that the decrease of the PKC activity may be resulted in decrease of phosphorylation of proteins binding to the 2. 5 kb fragment and expression of Ha-ras oncogene.These molecular events may play an important role in inhibition of proliferation of human gastric cancer cells by diterpene forskolin.