Zhao Ying, Lin Zixiang, Lin Zhaoyan, Zhou Chaoyu, Liu Gang, Lin Jiahao, Zhang Di, Lin Degui
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Animals (Basel). 2020 Dec 27;11(1):37. doi: 10.3390/ani11010037.
Mucin 1 (MUC1), a transmembrane protein, is closely associated with the malignancy and metastasis of canine mammary tumors; however, the role of overexpressed MUC1 in the development of cancer cells and response to drug treatment remains unclear. To address this question, we developed a new canine mammary tumor cell line, CIPp-MUC1, with an elevated expression level of MUC1. In vitro studies showed that CIPp-MUC1 cells are superior in proliferation and migration than wild-type control, which was associated with the upregulation of PI3K, p-Akt, mTOR, Bcl-2. In addition, overexpression of MUC1 in CIPp-MUC1 cells inhibited the suppressing activity of disulfiram on the growth and metastasis of tumor cells, as well as inhibiting the pro-apoptotic effect of disulfiram. In vivo studies, on the other side, showed more rapid tumor growth and stronger resistance to disulfiram treatment in CIPp-MUC1 xenograft mice than in wild-type control. In conclusion, our study demonstrated the importance of MUC1 in affecting the therapeutical efficiency of disulfiram against canine mammary tumors, indicating that the expression level of MUC1 should be considered for clinical use of disulfiram or other drugs targeting PI3K/Akt pathway.
黏蛋白1（MUC1）是一种跨膜蛋白，与犬乳腺肿瘤的恶性和转移密切相关；然而，过表达的MUC1在癌细胞发展和药物治疗反应中的作用仍不清楚。为了解决这个问题，我们开发了一种新的犬乳腺肿瘤细胞系CIPp-MUC1，其MUC1表达水平升高。体外研究表明，CIPp-MUC1细胞在增殖和迁移方面优于野生型对照，这与PI3K、p-Akt、mTOR、Bcl-2的上调有关。此外，CIPp-MUC1细胞中MUC1的过表达抑制了双硫仑对肿瘤细胞生长和转移的抑制活性，也抑制了双硫仑的促凋亡作用。另一方面，体内研究表明，CIPp-MUC1异种移植小鼠的肿瘤生长比野生型对照更快，对双硫仑治疗的抗性更强。总之，我们的研究证明了MUC1在影响双硫仑对犬乳腺肿瘤治疗效果方面的重要性，表明在双硫仑或其他靶向PI3K/Akt途径的药物临床应用中应考虑MUC1的表达水平。
