Natural compound Oblongifolin C confers gemcitabine resistance in pancreatic cancer by downregulating Src/MAPK/ERK pathways

作者：Li, Yang; Xi, Zhichao; Chen, Xiaoqiong; Cai, Shuangfan; Liang, Chen; Wang, Zhen; Li, Yingyi; Tan, Hongsheng; Lao, Yuanzhi^*; Xu, Hongxi^*

来源：Cell Death & Disease, 2018, 9(5): 538.

DOI：10.1038/s41419-018-0574-1

• SRC TYROSINE KINASE
• ACTIVE SRC
• CELLS
• ACTIVATION
• INHIBITION
• CARCINOMA
• GROWTH
• ADENOCARCINOMA
• HEAD
• DEGRADATION

Gemcitabine (GEM) induced drug resistance is the major reason for the failure of chemotherapy in pancreatic cancer (PC). In this study, we found that Oblongifolin C (OC) efficiently inhibited PC cell proliferation by inducing G0/G1 arrest and apoptosis. Also, our mechanism study demonstrated that OC re sensitized the GEM resistant PC cells through the ubiquitin-proteasome-dependent degradation of Src, and then downregulating the MAPK pathway. Knockdown of Src plus OC resulted in a greater inhibitory effect in GEM-resistant PC cells. In contrast, Src overexpression reversed OC-mediated chemosensitization, thereby implicating Src in the action of OC Moreover, our in vivo study showed that OC suppressed the tumor growth via the downregulation of Src, and enhanced the chemosensitivity of GEM resistant PC to GEM Overall, our results have revealed that OC is applicable as a promising agent for overcoming GEM resistant PC, especially with aberrant Src expression.

• 出版日期2018-5-10
• 单位上海中医药大学; 复旦大学