二甲胺四环素增强博安霉素的抗肿瘤转移作用  

MINOCYCLINE POTENTIATES THE ANTIMETASTATIC EFFECT OF BOANMYCIN

作　　者：刘建国[1] 江敏[1] 徐琳娜[1] 甄永苏[1] 

机构地区：[1]中国医学科学院,中国协和医科大学医药生物技术研究所

出　　处：《药学学报》1995年第9期668-673,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

摘　　要：博安霉素对小鼠Ｌｅｗｉｓ肺癌的肺转移有显著抑制作用；用等毒性剂量进行比较，博安霉素的肺转移抑制率高于丝裂霉素。单独给博安霉素（５ｍｇ·ｋｇ－１）对肺转移抑制率为６７％，对其中大转移瘤结（直径＞２ｍｍ）的抑制率为８５％；博安霉素与二甲胺四环素（５ｍｇ·ｋｇ－１）联合使用时，对肺转移瘤以及时大转移瘤结的抑制率分别为８８％和１００％，两药相互作用指数ＣＤＩ＜０．５（Ｐ＜０．０１），表明二甲胺四环素能明显增强博安霉素的抗转移作用。酶联免疫测定证明，二甲胺四环素能降低肺巨细胞癌ＰＧ细胞ＩＶ型胶原酶的表达，Ｆｕｒａ－２／ＡＭ荧光法测定，二甲胺四环素能显著降低ＰＧ细胞内游离Ｃａ２＋的水平。本研究结果提示博安霉素与二甲胺四环索联合用药可能有利于控制肿瘤转移，二甲胺四环素的增效机制可能与抑制ＩＶ型胶原酶的表达、干扰肿瘤侵袭与转移的过程有关。Boanmycin(bleomycin A6, BAM)was found to markedly inhibit the spontaneouspulmonary metastasis of Lewis carcinoma in mice.Compared at equitowic doses (1/9 LD50),BAMwas more effective than mitomycin。Minocycline (MNO)at 5 mg·kg-1 showed no inhibition on thegrowth of sc transplanted Lewis primary tumor; however, it markedly potentiated the antimetastaticeffect of BAM. Treated with BAM(5 mg· kg-1) alone,the number of total metastatic foci and thatof large foci (>2mm in diameter)in the lung were suppressed by 67%and 85%,respectively.When BAM was used in combination with MNO, the number of those foci was further reduced by88%and 100%, respectively.By NAG enzyme assay, MNO was not cytotoxic and showed nosynergism with BAM against PG cells, a cell line derived from a hlghly metastatic human giant cellcarcinoma of the lung.Determined by ELISA with a monoclonal antiboody,the expression of type IVcollagenase in PG cells was remarkably inhibited by MNO.The intracellular free Ca2+ level in PGcells was reduced from 76.7 nmol·L-1 to 42.2 nmol·L-1 by MNO treatment. The study suggeststhat the combination of boanmycin and minocycline may be useful for control of tumor metastasis andthe inhibition of type IV collagenase expression may be involved in the mechanism of minocyclinepotentiation.

关 键 词：博安霉素 二甲胺四环素 胶原酶 抗肿瘤转移 

分 类 号：R978.14[医药卫生—药品] R965.1[医药卫生—药学]