Cyclopamine Decreased the Expression of Sonic Hedgehog and its Downstream Genes in Colon Cancer Stem Cells

Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells. Materials and Methods: The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine. Results: HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner. Conclusion: Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.

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内容要旨・審査要旨 : LID201505251001.pdf
論文本文 : k2796_fulltext.pdf
本論文は,著者BAT-ERDENE BATSAIKHANの学位論文として提出され, 学位審査・授与の対象となっている。
著者の申請により要約(2015-05-25公開)に替えて論文全文を公開(2022-12-14)