title: Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models.
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.
authors.affiliation: Department of General Surgery, Tianjin Hospital, Tianjin, China (mainland).
authors.forename: Huifa
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Tianjin Hospital, Tianjin, China (mainland).
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Gastrointestinal Surgery, Nankai Hospital, Tianjin, China (mainland).
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D017239:Paclitaxel; D000072086:Smoothened Receptor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: C491023:SMO protein, human; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D017239:Paclitaxel