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: To verify the link between Shh/Smo signaling and the phenotypic alterations in GBCs, we used cyclopamine, an inhibitor of Smo. In contrast to rhShh, cyclopamine suppressed proliferation (Fig.4a) and invasiveness (Fig.4b) in GBd15 and TGBC2TKB cells. To exclude the possibility of a non-specific effect of cyclopamine, we also used Smo-targeting siRNA. Smo siRNA transfection decreased Smo expression by 90% and Gli1 expression by 70% (Fig. S1). Smo siRNA also significantly suppressed the proliferation (Fig.4c), and invasiveness (Fig.4d) of GBd15 and TGBC2TKB cells. These results suggest that Hh signaling can modulate the proliferative and invasive phenotypes of GBC cells and that Smo inhibition ameliorates the phenotype.
Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.