促吞噬肽tuftsin增强丝裂霉素和力达霉素的抗肿瘤活性  

Tuftsin Potentiates the Antitumor Activity of Mitomycin and Lidamycin

作　　者：刘文娟[1] 刘秀均[1] 甄永苏[1] 

机构地区：[1]中国医学科学院/北京协和医学院医药生物技术研究所,100050

出　　处：《医学研究杂志》2013年第5期26-30,共5页Journal of Medical Research

基　　金：国家重点基础研究发展计划("973"计划)基金资助项目(2009CB521807)

摘　　要：目的研究促吞噬肽(tuftsin,TF)与丝裂霉素(MMC)、力达霉素(LDM)联合的抑制肿瘤细胞增殖作用,以及tuftsin与力达霉素(LDM)整合成一个分子LDM-TF,并探讨其抗肿瘤活性。方法用MTT法检测tuftsin与不同浓度抗肿瘤药联合作用肿瘤细胞24h后,其体外抗细胞增殖作用。通过基因工程的方法构建了tuftsin与力达霉素辅基蛋白(LDP)的融合蛋白(LDP-TF),并进一步再通过加入发色团构建强化融合蛋白(LDM-TF)。用CCK-8法测LDP-TF蛋白的抗肿瘤活性,MTT法检测LDM-TF的体外抗肿瘤活性。结果 tuftsin单独作用肿瘤细胞体外抗增殖作用较弱。tuftsin与丝裂霉素(MMC)或力达霉素(LDM)联用均显示增效作用,其中以在胰腺癌SW1990细胞的增效作用最为显著。本实验室制备的融合蛋白LDP-TF和强化融合蛋白LDM-TF在体外对肿瘤细胞具有比力达辅基蛋白(LDP)和力达霉素(LDM)显示更强的抑制肿瘤细胞增殖作用。结论tuftsin在体外与丝裂霉素和力达霉素联合显示协同作用。基于tuftsin的整合分子LDP-TF和LDM-TF与LDP或LDM比较,具有更强的抗肿瘤活性。Objective To investigate the effect of tuftsin （TF） and its combination respectively with mitomycin （MMC） and lida- mycin （LDM） on various cancer cell lines. Furthermore, an engineered tuftsin - integrated lidamycin fusion protein has been prepared and its antitumor efficacy was investigated. Methods Cultured tumor cells were treated with tuftsin or the combination of tuftsin with che- motherapeutic agents, MMC and LDM. Cell viability was measured by MTT assay and ICs0 was calculated. By DNA recombination, TF was fused to the apoprotein （LDP） of lidamycin to obtain a fusion protein, LDP- TF. Then and the energized fusion protein LDM -TF was prepared by integrating the active chromopbore of lidamycin into the LDP - TF. CCK - 8 assay was used to measure the cytotoxicity of LDP - TF. MTT assay was used to measure the cytotoxicity of LDM - TF. Results TF alone showed mild cytotoxicity to various cancer cells. However, TF in combinations with MMC and LDM both showed synergy against cancer cells, in particular, the pancreatic carcinoma SW1990 cells. The fusion protein LDP - TF and the energized fusion protein LDM - TF exhibited more potent cytotoxicity to cancer cells as compared with LDP and LDM, respectively. Conclusion Tuftsin showes synergy with MMC and LDM. The integrated molecules, LDP - TF and LDM - TF, exert more potent cytotoxicity to cancer cells than LDP and LDM, respectively.

关 键 词：促吞噬肽 丝裂霉素 力达霉素 融合蛋白 联合 

分 类 号：R657.6[医药卫生—外科学]