文章标题：Yu Shi, Yan Wang, Jing Qian, Xiaodi Yan, Yong Han, Ninghua Yao, Jianbo Ma
影响因子：3.647
期刊：LIFE SCIENCES
作者列表：Li Li, Hongyan Zhu, Xiangyang Li, Yaoqi Ke, Shuai Yang, Qingping Cheng
发表时间：2020-7-25
DOI:10.1016/j.lfs.2020.118148
主要研究成果：Abstract
Pancreatic cancer is a malignant cancer with poor prognosis. This study aimed to explore how O6-methylguanine-DNA methyltransferase （MGMT） affects the gemcitabine resistance of pancreatic cancer cells by the regulatory role of SHH/GLI signaling pathway. MGMT inhibition induced by lomeguatrib （LM） suppressed the proliferation, invasion, migration ａnd autophagy, promoted the apoptosis of PanC-1/GEM cells ａnd up-regulated the GEM inhibition rates for PanC-1/GEM cells. Moreover, MGMT inhibition increased the expression of Caspase-3 ａnd Bax ａnd decreased the expression of Bcl-2, Beclin1 ａnd Atg5 in PanC-1/GEM cells. PVT1 silencing could also produce the similar effects of MGMT inhibition induced by LM on PanC-1/GEM cells. And, PVT1 silencing could inhibit the SHH/GLI signaling pathway in PanC-1/GEM cells by regulating the MGMT expression. miR-409 was demonstrated to be a potential target of PVT1 ａnd SHH was demonstrated to be a potential target of miR-409. Furthermore, GLI overexpression could reverse the effects of PVT1 silencing. In the xenograft model of pancreatic cancer, nude mice were treated with GEM. MGMT inhibition suppressed the tumor growth ａnd autophagy ａnd promoted the apoptosis in tumor tissues. And, PVT1 silencing could inhibit the SHH/GLI signaling pathway in tumor tissues. In conclusion, MGMT inhibition could suppress the proliferation, invasion, migration ａnd autophagy ａnd promote the apoptosis of PanC-1/GEM cells in vitro ａnd in vivo. PVT1 silencing may affect the PanC-1/GEM cells through changing the MGMT expression by inhibiting the SHH/GLI signaling pathway.
