Related Experiment Video
Updated: May 16, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Mechanism of CRM1 Inhibition by Lansoprazole and Its Synergy with Cisplatin in Gastric Cancer
Yubin Luo1,2, Qiaohua Yan1, Bingzhou Huang1
1Department of Pulmonary and Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610032, China.
Abstract:
CRM1 (Chromosome Region Maintenance 1, also known as Exportin-1 or XPO1) is a key nuclear export factor that exports and inactivates tumor suppressor proteins in cancer. Here, we report that the proton pump inhibitor lansoprazole, upon acid activation, is converted into a CRM1 inhibitor in vitro. The active component is a positively charged molecule that binds noncovalently to the nuclear export signal (NES) groove of CRM1, as revealed by biochemical studies and a 2.0 Å cocrystal structure. Interestingly, lansoprazole undergoes spontaneous activation in cells, thereby inhibiting nuclear export to a similar extent as its preacid-activated form. Since the compound is susceptible to inhibition by glutathione (GSH), we designed a combination strategy where cisplatin, by depleting GSH, synergistically enhanced CRM1 inhibition. This combination demonstrated antitumor synergy in a gastric cancer xenograft model without increasing toxicity. Our work presents a novel CRM1 inhibitor and a chemosensitization strategy for gastric cancer.
Related Concept Videos
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Drugs for Peptic Ulcer Disease: Sucralfate as Mucosal Protective Agents
In this scenario, mucosal protective agents like sucralfate play an essential role. Sucralfate, a complex of sulfated sucrose and aluminum hydroxide, demonstrates its usefulness in acidic conditions,...
Abnormal Proliferation
Treatment Resistant Cancers