Cyclopamine increases the cytotoxic effects of paclitaxel and radiation but not cisplatin and gemcitabine in Hedgehog expressing pancreatic cancer cells

Abstract

These data suggest strategies to combine Hh inhibitors with radiotherapy and chemotherapeutic agents, specifically paclitaxel and related compounds in the treatment of pancreatic cancer.

Pancreatic cancer stem cells: new understanding of tumorigenesis, clinical implications

“…The same effect was found in human pancreatic cancer cells PANC-1, SUIT-2, and AsPC-1, when cyclopamine and EGFR inhibitor were combined [54]. Furthermore, cyclopamine was shown to increase the cytotoxic effects of paclitaxel and radiation therapy in human pancreatic cancer cells MiaPaCa-2, BxPC-3, and HCT116 [55]. Unpublished data from our research group also suggest that treatment of different pancreatic cancer cell lines with cyclopamine (alone or in combination with 5-FU) reduces the amount of SP cells and, most interestingly, restores the acquired 5-Fluorouracil-induced chemoresistance in AsPC-1 and L3.6pl pancreatic cancer cell lines in vitro.…”

Expression and regulation of hedgehog signaling pathway in pancreatic cancer

“…A recent study through transgenic mouse model indicated that the cooperation of Hh and Ras signaling was crucial during the earliest stages of PDA formation [15], and the overexpression of Shh in pancreatic cancer stem cells (CSCs) showed that Hh signaling might play a role in the regulation of self-renewal and resistance to chemoradiation in pancreatic CSCs [16]. Furthermore, the therapeutic effects through the blockade of Hh pathway support that Hh signaling represents possible target of new treatment strategies for pancreatic cancer [17][18][19]. However, in a latest study, Nolan-Stevaux and his colleagues reported that autocrine Shh-Ptch-Smo signaling was not required in pancreatic ductal cells for PDAC progression, since the deletion of Smo in the pancreas failed to affect the multistage development of PDAC tumors.…”

Identification of Cancer Stem Cell–Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line

“…Cytokines are indispensable markers for classification of poorly differentiated or phenotypically ''deviant'' tumors. Cytokines 8,18, and 19 are prevalent in squamous cell carcinoma, and specific antibodies against them aid in diagnosing NPC. To determine whether there were expression differences in the three cytokines between SP and NSP cells, freshly sorted cells were grown on sterile glass cover slides overnight at 37jC, washed twice with PBS, and fixed in 4% paraformaldehyde for 30 min at 4jC.…”