Center for Biological Systems Analysis ZBSA, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
Department of General- and Visceral Surgery, University of Freiburg Medical Center Faculty of Medicine, 79106 Freiburg, Germany.
Cells. 2020 May 19;9(5):1251. doi: 10.3390/cells9051251.
Pancreatic ductal adenocarcinoma (PDAC) correlates with high mortality and is about to become one of the major reasons for cancer-related mortality in the next decades. One reason for that high mortality is the limited availability of effective chemotherapy as well as the intrinsic or acquired resistance against it. Here, we report the impact of nab-paclitaxel on the cellular metabolome of PDAC cell lines. After establishment of nab-paclitaxel resistant cell lines, comparison of parental and resistant PDAC cell lines by metabolomics and biochemical assessments revealed altered metabolism, enhanced viability and reduced apoptosis. The results unveiled that acute nab-paclitaxel treatment affected primary metabolism to a minor extent. However, acquisition of resistance led to altered metabolites in both cell lines tested. Specifically, aspartic acid and carbamoyl-aspartic acid were differentially abundant, which might indicate an increased de novo pyrimidine synthesis. This pathway has already shown a similar behavior in other cancerous entities and thus might serve in the future as vulnerable target fighting resistance acquisition occurring in common malignancies.
胰腺导管腺癌（PDAC）与高死亡率相关，并且即将成为未来几十年癌症相关死亡的主要原因之一。导致这种高死亡率的一个原因是有效的化疗药物的可用性有限，以及对这些化疗药物的内在或获得性耐药性。在这里，我们报告了 nab-紫杉醇对 PDAC 细胞系细胞代谢组的影响。在建立 nab-紫杉醇耐药细胞系后，通过代谢组学和生化评估比较亲本和耐药 PDAC 细胞系，发现代谢发生改变，细胞活力增强，细胞凋亡减少。结果表明，急性 nab-紫杉醇处理对初级代谢的影响较小。然而，获得耐药性导致两种测试细胞系中的代谢物发生改变。具体而言，天冬氨酸和氨甲酰天冬氨酸的丰度不同，这可能表明从头嘧啶合成增加。这条途径在其他癌症实体中已经表现出类似的行为，因此将来可能作为对抗常见恶性肿瘤中耐药性获得的脆弱靶点。
