Gemcitabine Alters Phosphatidylcholine Metabolism in Mouse Pancreatic Tumors.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest diseases, despite advancements in elucidating tumor biology and developing novel therapeutics. Importantly, lipids, such as phospholipids, are crucial for the survival and proliferation of tumor cells. However, the impact of chemotherapeutic drugs on phospholipid metabolism in PDAC remains poorly understood. Gemcitabine (a nucleoside analogue) is a first-line drug in PDAC treatment, but its clinical effectiveness is limited by multiple factors. Herein, we employed matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and proteomics approaches to investigate gemcitabine-induced lipid metabolism alterations in mouse pancreatic tumors following gemcitabine treatment (n = 3, control tumors; n = 3, gemcitabine-treated tumors). From MALDI MSI experiments, we observed elevated levels of several phosphatidylcholines (PCs), PC(30:0), PC(32:3), PC(34:2), PC(36:1), and PC(36:2), in gemcitabine-treated tumor tissues compared to the control. In addition, proteomics data revealed the differential abundance of several phospholipid-binding proteins in response to gemcitabine treatments. Furthermore, several endoplasmic reticulum stress-related proteins exhibited high expression in gemcitabine-treated tumor tissues. Altogether, our MALDI MSI and proteomics data provide important insights into alterations in PC metabolism in pancreatic tumors in response to gemcitabine treatment. Importantly, targeting the altered PC metabolism during gemcitabine therapy might help combat pancreatic cancer.