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在实验模型中，靶向 smoothened 可使胃癌对化疗敏感。

Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models.

作者信息

Ma Huifa, Tian Yongsheng, Yu Xiangyang

机构信息

Department of General Surgery, Tianjin Hospital, Tianjin, China (mainland).

Department of Gastrointestinal Surgery, Nankai Hospital, Tianjin, China (mainland).

出版信息

Med Sci Monit. 2017 Mar 28;23:1493-1500. doi: 10.12659/msm.903012.

DOI:10.12659/msm.903012
PMID:28350784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5381338/
Abstract

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 AND 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.

摘要

背景 刺猬信号通路受体 smoothened（SMO）在肿瘤进展中起关键作用。然而，SMO 是否为调节胃癌化疗耐药性的关键因素尚不清楚。材料与方法 我们在临床样本、胃癌细胞系（424GC 和 AGS）以及皮下同基因小鼠模型中研究了 SMO 在诱导胃癌紫杉醇耐药中的潜在作用。结果 我们发现紫杉醇耐药胃癌临床样本中 SMO 表达较高。紫杉醇处理的胃癌细胞比药物敏感细胞具有更高的 SMO 表达。上调 SMO 表达通过增强细胞增殖和抑制凋亡诱导胃癌细胞系产生紫杉醇耐药。SMO 抑制剂 IPI-926 与紫杉醇联合使用可降低体外紫杉醇耐药胃癌细胞的活力，并在动物模型中控制肿瘤生长。结论 刺猬信号通路受体 SMO 是胃癌紫杉醇耐药的重要调节因子，可能是使紫杉醇耐药肿瘤敏感化的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3495/5381338/6de613e3649f/medscimonit-23-1493-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3495/5381338/6de613e3649f/medscimonit-23-1493-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3495/5381338/bb11088b0bb1/medscimonit-23-1493-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3495/5381338/6ee9572a8b6f/medscimonit-23-1493-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3495/5381338/3013f5a9926f/medscimonit-23-1493-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3495/5381338/6de613e3649f/medscimonit-23-1493-g004.jpg

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