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Cyclopamine reverts acquired chemoresistance and down-regulates cancer stem cell markers in pancreatic cancer cell lines
发布时间:2016-11-28   浏览次数:967

Abstract

BACKGROUND:The hedgehog (Hh) pathway has been implicated inthe pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC).Recent studies have suggested that Hh plays an important role in maintainingthe cancer stem cell (CSCs) pool. Gemcitabine-resistant pancreatic cancer cellshighly express some of the CSCs markers. However, the expression level of Hhmembers in gemcitabine-resistant pancreatic cancer cells remains unknown. Theaim of this study was to verify the expression of HH members, such as Shh, Ptc,SMO and Gli-1 in gemcitabine-resistant PDAC cell lines, and to explore a newstrategy to overcome chemoresistance in PDAC.

MATERIALAND METHODS: Quantitative real-time RT-PCR (Q-PCR)and western blot were used to evaluate the relative expression level of HHmembers in SW1990, CFPAC-1 cells and gemcitabine-resistant SW1990, CFPAC-1cells. The change of cancer stem cell markers and the expression level of HHmembers before and after cyclopamine treatment was evaluated using flowcytometry and Q-PCR, western blot, respectively. Cell apoptosis aftercyclopamine treatment was measured by flow cytometry.

RESULTS:CD44, CD133 and the expression level of HH members,including Shh, SMO, Gli-1, were found to be highly expressed ingemcitabine-resistant cells, which were significantly down-regulated bycyclopamine treatment. Flow cytometry analysis showed increased cell apoptosisafter cyclopamine treatment.

CONCLUSION:Gemcitabine-resistant pancreatic cancer cellshighly express CSCs markers and some of the HH members, and inhibition of HH bycyclopamine is an effective method of reversing gemcitabine resistance inpancreatic cancer.