Mcl-1 inhibitor suppresses tumor growth of esophageal squamous cell carcinoma in a mouse model

作者：Lin, Jianqing; Fu, Deqiang; Dai, Yijun; Lin, Jianguang; Xu, Tianwen^*

来源：Oncotarget, 2017, 8(70): 114457-114462.

DOI：10.18632/oncotarget.18772

• ESCC
• Mcl-1
• A-1210477

Esophageal squamous cell carcinoma (ESCC) has a high morbidity in China, accounting for 90% of all esophageal carcinoma cases. Hence, identifying drug targets for prevention and treatment of ESCC is essential. Due to its critical role in the regulation of cell apoptosis, Mcl-1 holds great potential as a target for treatment against ESCC. In current study, we used a 4-nitroquinoline-1-oxide (4-NQO)-induced ESCC mouse model of test whether A-1210477, a Mcl-1 small molecular inhibitor, could repress ESCC development. We showed that A-1210477 treatment decreased ESCC formation and animal weight loss in a dose dependent manner. We detected decreased cellular proliferation in A-1210477-treated ESCC tissue by Ki67 expression. Moreover, A-1210477 treatment increased the number of apoptotic cells in ESCC tissues. Our study clearly demonstrates the contribution of Mcl-1 to ESCC development through promoting cell proliferation and inhibition of apoptosis, and provides a strong evidence for further evaluation of A-1210477 for treating ESCC.

• 出版日期2017-12-29
• 单位福建医科大学