Curcumin Derivative C66 Suppresses Pancreatic Cancer Progression through the Inhibition of JNK-Mediated Inflammation

Molecules

卷:27

Xiong Chen¹  Jie Deng²  Zheng Xu²  Qinbo Chen²  Rongdiao Liu²  Guang Liang³  Lingfeng Chen³  Yuchen Jiang⁴  Hongjin Chen⁵ 

[1] Department of Endocrinology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China;

[2] Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China;

[3] School of Pharmacy, Hangzhou Medical College, Hangzhou 310000, China;

[4] The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China;

[5] Translational Medicine Research Center, Guizhou Medical University, Guiyang 550000, China;

关键词: C66;    pancreatic cancer;    inflammation;    JNK;   

DOI  :  10.3390/molecules27103076

来源: DOAJ

【 摘 要 】

Pancreatic adenocarcinoma is by far the deadliest type of cancer. Inflammation is one of the important risk factors in tumor development. However, it is not yet clear whether deterioration in pancreatic cancer patients is related to inflammation, as well as the underlying mechanism. In addition, JNK is abnormally activated in pancreatic cancer cells and the JNK inhibitor C66 reduces the inflammatory microenvironment in the tumor. Therefore, the aim of this study was to evaluate the role of C66 in the proliferation and migration of pancreatic cancer. Our results showed that various inflammatory cytokines, such as IL-1β, IL-6, IL-8, and IL-15, were more expressed in pancreatic cancer than in the matching normal tissue. Furthermore, C66, a curcumin analogue with good anti-inflammatory activity, inhibited the proliferation and migration of pancreatic cancer cells in a dose-dependent manner, and effectively inhibited the expression of the above inflammatory factors. Our previous research demonstrated that C66 prevents the inflammatory response by targeting JNK. Therefore, in this study, JNK activity in pancreatic cancer cells was investigated, revealing that JNK was highly activated, and the treatment with C66 inhibited the phosphorylation of JNK. Next, shJNK was used to knockdown JNK expression in pancreatic cancer cells to further confirm the role of JNK in the proliferation and migration of this tumor, as well as in the inflammatory tumor microenvironment (TME). The results demonstrated that JNK knockdown could significantly inhibit the proliferation and migration of pancreatic cancer. Moreover, the low JNK expression in pancreatic cancer cells significantly inhibited the expression of various inflammatory factors. These results indicated that C66 inhibited the progression of pancreatic cancer through the inhibition of JNK-mediated inflammation.

【 授权许可】

Unknown