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Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer.

Matsushita S, Onishi H, Nakano K, Nagamatsu I, Imaizumi A, Hattori M, Oda Y, Tanaka M, Katano M - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

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Related in: MedlinePlus

Cyclopamine (Cyclo) and Smo siRNA suppress proliferative and invasive phenotypes of gallbladder cancer cells. (a) GBd15 and TGBC2TKB cells were seeded onto 96-well plates and incubated with cyclopamine (at 5, 10, or 20 μM) for 24, 48, or 72 h. (b) GBd15 and TGBC2TKB cells were incubated for 16 h in the presence or absence of cyclopamine (at 5 or 10 μM). Migrated cells were quantified by bright-field microscopy. (c) GBd15 and TGBC2TKB cells were transfected with Smo siRNA (siSmo) and incubated for 24, 48, or 72 h. (d) GBd15 and TGBC2TKB cells were transfected with Smo siRNA and incubated for 16 h. Migrated cells were quantified by bright-field microscopy. Error bars represent standard deviations. *P < 0.05. siCont, control siRNA.
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fig04: Cyclopamine (Cyclo) and Smo siRNA suppress proliferative and invasive phenotypes of gallbladder cancer cells. (a) GBd15 and TGBC2TKB cells were seeded onto 96-well plates and incubated with cyclopamine (at 5, 10, or 20 μM) for 24, 48, or 72 h. (b) GBd15 and TGBC2TKB cells were incubated for 16 h in the presence or absence of cyclopamine (at 5 or 10 μM). Migrated cells were quantified by bright-field microscopy. (c) GBd15 and TGBC2TKB cells were transfected with Smo siRNA (siSmo) and incubated for 24, 48, or 72 h. (d) GBd15 and TGBC2TKB cells were transfected with Smo siRNA and incubated for 16 h. Migrated cells were quantified by bright-field microscopy. Error bars represent standard deviations. *P < 0.05. siCont, control siRNA.

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.


Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer.

Matsushita S, Onishi H, Nakano K, Nagamatsu I, Imaizumi A, Hattori M, Oda Y, Tanaka M, Katano M - Cancer Sci. (2014)

Cyclopamine (Cyclo) and Smo siRNA suppress proliferative and invasive phenotypes of gallbladder cancer cells. (a) GBd15 and TGBC2TKB cells were seeded onto 96-well plates and incubated with cyclopamine (at 5, 10, or 20 μM) for 24, 48, or 72 h. (b) GBd15 and TGBC2TKB cells were incubated for 16 h in the presence or absence of cyclopamine (at 5 or 10 μM). Migrated cells were quantified by bright-field microscopy. (c) GBd15 and TGBC2TKB cells were transfected with Smo siRNA (siSmo) and incubated for 24, 48, or 72 h. (d) GBd15 and TGBC2TKB cells were transfected with Smo siRNA and incubated for 16 h. Migrated cells were quantified by bright-field microscopy. Error bars represent standard deviations. *P < 0.05. siCont, control siRNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4317941&req=5

fig04: Cyclopamine (Cyclo) and Smo siRNA suppress proliferative and invasive phenotypes of gallbladder cancer cells. (a) GBd15 and TGBC2TKB cells were seeded onto 96-well plates and incubated with cyclopamine (at 5, 10, or 20 μM) for 24, 48, or 72 h. (b) GBd15 and TGBC2TKB cells were incubated for 16 h in the presence or absence of cyclopamine (at 5 or 10 μM). Migrated cells were quantified by bright-field microscopy. (c) GBd15 and TGBC2TKB cells were transfected with Smo siRNA (siSmo) and incubated for 24, 48, or 72 h. (d) GBd15 and TGBC2TKB cells were transfected with Smo siRNA and incubated for 16 h. Migrated cells were quantified by bright-field microscopy. Error bars represent standard deviations. *P < 0.05. siCont, control siRNA.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Show MeSH
Related in: MedlinePlus