Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer.
Bottom Line: New effective therapeutic strategies are greatly needed.In contrast, inhibiting the effector Smo decreased the anchor-dependent and anchor-independent proliferation.These results suggest that Hh signaling is elevated in GBC and may be involved in the acquisition of malignant phenotypes, and that Hh signaling may be a potential therapeutic target for GBC.
Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Show MeSH
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Mentions: We next investigated the role of Hh signaling on anchorage-independent growth of GBC cells. The addition of rhShh significantly enhanced colony formation, an anchorage-independent phenotype, in GBd15 and TGBC2TKB cells (Fig.7a). Cyclopamine and Smo siRNA also significantly suppressed colony formation in GBd15 and TGBC2TKB cells (Fig.7b,c). These results indicate that Hh signaling affects anchorage-independent growth in GBC cells. To determine whether the observed changes induced by Hh signaling in cells is reflected in vivo, we investigated the tumorigenicity of GBC cells transfected with Smo siRNA in athymic nude mice. Subcutaneous tumors developed in three out of five mice injected with cells transfected with Smo siRNA. In contrast, all of the five mice injected with control siRNA transfected cells showed tumor development (Fig.7d). There were significant differences in tumor growth/size between Smo siRNA and control siRNA groups as well (Fig.7e). Furthermore, we confirmed that the expression of Gli1 and Smo in Smo siRNA transfected GBC cells were lower than in the controls (Fig.7f).
Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.