Gu Lian-Zhi, Hu Wen-Yang, Antic Nenad, Mehta Rajendra, Turner Jerrold R, de Lanerolle Primal
Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, 835 South Wolcott Ave, Chicago, IL 60612-7342, USA.
Eur J Cancer. 2006 May;42(7):948-57. doi: 10.1016/j.ejca.2005.12.017. Epub 2006 Mar 30.
We have previously shown that ML-7, which inhibits myosin light chain kinase (MLCK), induces apoptosis in transformed and non-transformed cells. We have extended these studies and found that ML-7 stimulates the ability of etoposide to induce apoptosis in Mm5MT mouse mammary adenocarcinoma cells and Mat-Ly-Lu rat prostate cancer cells in vitro. ML-7 was also found to have a chemopreventive effect using an in vitro mouse mammary organ culture model. In vivo experiments demonstrated that ML-7 retards the growth of mammary tumours in mice and prostate tumours in rats. Moreover, ML-7 significantly stimulates the ability of etoposide to prevent the growth of established mammary tumours in mice and prostate tumours in rats. These results provide evidence for the efficacy of ML-7 as an adjuvant to etoposide in these models and warrants further development.
我们之前已经表明,抑制肌球蛋白轻链激酶(MLCK)的ML-7可在转化细胞和未转化细胞中诱导凋亡。我们扩展了这些研究,发现ML-7可增强依托泊苷在体外诱导Mm5MT小鼠乳腺腺癌细胞和Mat-Ly-Lu大鼠前列腺癌细胞凋亡的能力。使用体外小鼠乳腺器官培养模型还发现ML-7具有化学预防作用。体内实验表明,ML-7可延缓小鼠乳腺肿瘤和大鼠前列腺肿瘤的生长。此外,ML-7可显著增强依托泊苷预防小鼠已形成的乳腺肿瘤和大鼠前列腺肿瘤生长的能力。这些结果为ML-7作为依托泊苷在这些模型中的佐剂的有效性提供了证据,并值得进一步开发。