Хавдрын үүдэл эсийн зохицуулгад “sonic hedgehog” дохиоллын үүрэг / Шинэ санаа Шинэ нээлт

ABSTRACT

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigenic capacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs. METHODS: Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for 14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44, EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJ genes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM). RESULTS: The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathway Ptch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal marker Vimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited. CONCLUSION: EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.