小檗胺衍生物(EBB)体外抑制肺癌细胞增殖机制的初探

PRELIMINARY INVESTIGATION ON THE MECHANISM OF ANTICANCER BY BERBAMINE DERIVATIVE(EBB)IN VITRO

本文研究并发现了新型半天然钙调素(CaM)拮抗剂——O-4-乙氧基丁基小檗胺(O-4-ethoxy-butyl-berbamine,EBB),具有选择性抑制肺巨细胞癌(PG)的增殖和降低细胞内CaM水平的能力,对人胚肺细胞(HEL)的增殖和细胞内CaM的水平影响较小。同时观察到EBB引起肿瘤细胞内CaM水平降低的原因,是对CaM基因的转录产物(mRNA)和翻译产物(CaM)两方面作用的结果。此外,EBB还能部分降低PG细胞内原癌基因和突变的抑癌基因转录产物mRNA的水平。EBB抑制肿瘤细胞增殖的机制,除了对CaM基因的表达水平和CaM活性调控外,可能还直接或间接地影响了相关的原癌基因和突变的抑癌基因的表达。

In this paper, the inhibitory mechanism of tumor cell proliferation by a derivative berhamine (o-4-ethoxl-butyl-berbamine,EBB)has been studied.Experimental results showed that EBB as a new and strong CaM antagonist, inhibited proliferation of human lung cancer cells(PG)and had no significant toxic effect on normal lung cells(HEL). EBB inhibited the expression of CaM gene on the transcription and translation level. It can also inhibit the expression of oncogene(c-myc and c-H-ras)in PG cells, and reverse proliferation of the malignant lung cancer cells(PG)due to high mutation frequency of p53 and Rb genes.