Simvastatin targets pancreatic cancer stem-like cells and sensitizes PDA cells to chemotherapeutic drugs via sonic hedgehog signaling (original) (raw)

Pancreatic ductal adenocarcinoma (PDA) is a disease with an exceptionally poor prognosis, high therapy resistance and poor effective therapeutic options. Advances in therapeutic treatments are urgently required. Cancer stem-like cells (CSCs), capable of unlimited self-renewal, have been proposed as a mechanism for cancer growth, therapy resistance and metastasis, involving PDA. Besides a function in normal tissue development, Sonic hedgehog (Shh) is highly expressed at all stages of human PDA. Recent data demonstrate that the expression of Shh is highly upregulated in CSCs and regulates them. Simvastatin, which is widely prescribed as cholesterol-lowering drug, was shown to inhibit tumor growth, metastasis and cancer-specific mortality in some studies, but the available data are not consistent. Most importantly, the hypothesis of my thesis, namely that simvastatin attacks pancreatic CSCs by inhibition of Sonic hedgehog signaling was never examined before. In my thesis, I evaluated t...