Wakai K, Ohmura E, Satoh T, Murakami H, Isozaki O, Emoto N, Demura H, Shizume K, Tsushima T
Institute for Growth Science, Tokyo Women's Medical College, Japan.
Life Sci. 1994;54(11):703-9. doi: 10.1016/0024-3205(94)90158-9.
Semisynthetic tetracyclines (TCNs) are used for the management of malignant pleural effusions as sclerosing agents. However, their precise mechanism of actions are uncertain. In the present study, the mechanism of inhibitory effects of minocycline (MINO) and doxycycline (DOXY), on the accumulation of ascitic fluid induced by mouse fibrosarcoma (Meth-A) cells were investigated using male mice. Meth-A cells inoculated intraperitoneally elicited 2.5-4 ml of bloody ascites 10 days after implantation. The production of ascitic fluid was suppressed in a dose-related manner by daily intraperitoneal injections of MINO or DOXY, whereas vehicle (normal saline with 0.01N HCl) did not exert a significant effect. The inhibitory activity of these two substances was quite similar; one mg/mouse of MINO or DOXY inhibited the accumulation of fluid by 87% and 84%, respectively. The survival rate of Meth-A-bearing mice treated with MINO or DOXY was higher than that of the controls. Macroscopic examination of the peritoneal cavity did not reveal any obvious effects, such as adhesions, in mice treated with either MINO or DOXY. In vitro studies showed that MINO and DOXY suppressed Meth-A cell growth with IC50s of 5 microM and 8 microM, respectively. Maximal suppression (95%) was achieved at MINO and DOXY concentrations of 25 microM. The above observations suggest that MINO and DOXY inhibit the accumulation of ascites by a direct effect on Meth-A cell growth. Therefore, it appears that TCNs injected into the pleural cavity to manage malignant effusions in man exert their activity, at least in part, by suppressing malignant cell growth.
半合成四环素（TCNs）作为硬化剂用于治疗恶性胸腔积液。然而，其确切的作用机制尚不清楚。在本研究中，使用雄性小鼠研究了米诺环素（MINO）和多西环素（DOXY）对小鼠纤维肉瘤（Meth-A）细胞诱导的腹水积聚的抑制作用机制。腹腔接种的Meth-A细胞在植入后10天可引起2.5 - 4毫升血性腹水。每天腹腔注射MINO或DOXY可剂量相关地抑制腹水产生，而赋形剂（含0.01N HCl的生理盐水）则无显著作用。这两种物质的抑制活性非常相似；每只小鼠1毫克的MINO或DOXY分别抑制液体积聚87%和84%。用MINO或DOXY治疗的荷Meth-A小鼠的存活率高于对照组。对用MINO或DOXY治疗的小鼠腹腔进行宏观检查未发现任何明显影响，如粘连。体外研究表明，MINO和DOXY分别以5 microM和8 microM的IC50抑制Meth-A细胞生长。在MINO和DOXY浓度为25 microM时达到最大抑制（95%）。上述观察结果表明，MINO和DOXY通过直接影响Meth-A细胞生长来抑制腹水积聚。因此，似乎注入胸腔以治疗人类恶性胸腔积液的TCNs至少部分通过抑制恶性细胞生长发挥其作用。
