胰腺癌是癌症死亡的主要原因之一，其中胰腺导管腺癌（PDAC）是最常见的亚型。 PDAC 的晚期诊断很常见，导致治疗机会有限。吉西他滨是一种常用的化疗药物，可作为单一疗法或联合使用。然而，肿瘤常常对吉西他滨产生耐药性。先前的研究表明，与匹配的正常组织相比，PDAC 中的原癌基因 PIM 激酶（PIM1 和 PIM3）表达上调，并且与化疗耐药和 PDAC 细胞生长相关。 PIM 激酶还参与 PI3K/AKT/mTOR 通路以促进细胞存活。在本研究中，我们评估了新型多激酶 PIM/PI3K/mTOR 抑制剂 AUM302 和市售 PIM 抑制剂 TP-3654 的效果。使用五种人类 PDAC 细胞系，我们发现 AUM302 是细胞增殖、细胞活力、细胞周期进程和磷蛋白表达的有效抑制剂，而 TP-3654 效果较差。值得注意的是，AUM302 对吉西他滨耐药的 PDAC 细胞的活力有很大影响。综上所述，这些结果表明 AUM302 在人 PDAC 细胞中表现出抗肿瘤活性，因此有可能成为 PDAC 治疗的有效药物。版权所有：© 2023 Ingle 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Pancreatic cancer is one of the leading causes of cancer deaths, with pancreatic ductal adenocarcinoma (PDAC) being the most common subtype. Advanced stage diagnosis of PDAC is common, causing limited treatment opportunities. Gemcitabine is a frequently used chemotherapeutic agent which can be used as a monotherapy or in combination. However, tumors often develop resistance to gemcitabine. Previous studies show that the proto-oncogene PIM kinases (PIM1 and PIM3) are upregulated in PDAC compared to matched normal tissue and are related to chemoresistance and PDAC cell growth. The PIM kinases are also involved in the PI3K/AKT/mTOR pathway to promote cell survival. In this study, we evaluate the effect of the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, and commercially available PIM inhibitor, TP-3654. Using five human PDAC cell lines, we found AUM302 to be a potent inhibitor of cell proliferation, cell viability, cell cycle progression, and phosphoprotein expression, while TP-3654 was less effective. Significantly, AUM302 had a strong impact on the viability of gemcitabine-resistant PDAC cells. Taken together, these results demonstrate that AUM302 exhibits antitumor activity in human PDAC cells and thus has the potential to be an effective drug for PDAC therapy.Copyright: © 2023 Ingle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.