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Published: 2017-03-28

Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models

Huifa Ma, Yongsheng Tian, Xiangyang Yu

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

Med Sci Monit 2017; 23:1493-1500

DOI: 10.12659/MSM.903012


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.

Keywords: Antineoplastic Agents, Drug Resistance, Hedgehog Proteins, Stomach Neoplasms




Published: 2017-03-28

Dynamics of Fukuoka Criteria and Patient Management in Pancreatic Intraductal Papillary Mucinous Neoplasm...


Barbara Schellhaas, Francesco Vitali, Dane Wildner, Rüdiger S. Görtz, Lukas Pfeifer, Peter C. Konturek, Markus F. Neurath, Deike Strobel

Med Sci Monit 2017; 23:1483-1492

DOI: 10.12659/MSM.900535

Published: 2017-03-27

Sirtuin 1 (Sirt1) Overexpression in BaF3 Cells Contributes to Cell Proliferation Promotion, Apoptosis Res...


Qian Wang, Chao Yan, Miaomiao Xin, Li Han, Yunqing Zhang, Mingshu Sun

Med Sci Monit 2017; 23:1477-1482

DOI: 10.12659/MSM.900754