Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models

被引：7
作者：
Ma, Huifa [1 ]
Tian, Yongsheng [1 ]
Yu, Xiangyang [2 ]
机构：
[1] Tianjin Hosp, Dept Gen Surg, Tianjin, Peoples R China
[2] Nankai Hosp, Dept Gastrointestinal Surg, Tianjin, Peoples R China
来源：
MEDICAL SCIENCE MONITOR | 2017年 / 23卷
关键词：
Antineoplastic Agents; Drug Resistance; Hedgehog Proteins; Stomach Neoplasms; GROWTH-INHIBITION; PATHWAY; CELL; MEDULLOBLASTOMA; PROLIFERATION; RESISTANCE;
D O I：
10.12659/MSM.903012
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Background: The Hedgehog pathway receptor smoothened (SMO) has critical roles in tumor progression. However, whether SMO is a key factor regulating gastric cancer chemotherapy resistance is unknown. Material/ Methods: We investigated the potential functions of SMO in inducing gastric cancer paclitaxel resistance in clinical samples, gastric cancer cell lines (424GC and AGS), and subcutaneous syngeneic mouse models. Results: We found high SMO expression in paclitaxel-resistant gastric cancer clinical samples. Paclitaxel gastric cancer cells had higher SMO expression than in drug-sensitive cells. Upregulating SMO expression induced paclitaxel resistance in gastric cells lines via enhancing cell proliferation and inhibiting apoptosis. The combination of IPI-926, an inhibitor of SMO, with paclitaxel decreased cell viability of paclitaxel-resistant gastric cancer cells in vitro and controlled tumor growth in animal models. Conclusions: The Hedgehog pathway receptor SMO is an important regulator of gastric cancer paclitaxel resistance and could be a target for sensitizing paclitaxel-resistant tumors.
引用
收藏
页码：1493 / 1500
页数：8
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