Kurdyn Agnieszka, Paluszkiewicz Ewa, Augustin Ewa
Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdańsk, Poland.
Int J Mol Sci. 2025 Aug 5;26(15):7557. doi: 10.3390/ijms26157557.
Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis, requiring innovative approaches to evaluate new therapies. Considering the high activity of unsymmetrical bisacridines (UAs) in PC monolayer cultures, we employed multicellular tumor spheroids (MCTS) to assess whether UAs retain pro-apoptotic activity under more physiologically relevant conditions. Ultra-low attachment plates were used to form spheroids from three PC cell lines (Panc-1, MIA PaCa-2, and AsPC-1) with different genotypes and phenotypes. The effects of UA derivatives (C-2028, C-2045, and C-2053) were evaluated using microscopy and flow cytometry (7-AAD for viability and annexin V-FITC/PI for membrane integrity). UAs altered the morphology of the spheroids and reduced their growth. Notably, Panc-1 spheroids exhibited compromised integrity. The increase in 7-AAD cells confirmed diminished cell viability, and annexin V-FITC assays showed apoptosis as the dominant death pathway. Interestingly, the exact derivative was most active against a given cell line regardless of culture conditions. These results confirm that UAs maintain anticancer activity in 3D cultures and induce apoptosis, with varying efficacy across different cell lines. This underscores the value of diverse cellular models in compound evaluation and supports UAs as promising candidates for pancreatic cancer therapy.
胰腺癌（PC）是一种侵袭性恶性肿瘤，预后较差，需要创新方法来评估新疗法。鉴于不对称双吖啶（UAs）在胰腺癌单层培养中具有高活性，我们采用多细胞肿瘤球体（MCTS）来评估UAs在更接近生理条件下是否保留促凋亡活性。使用超低附着板从三种具有不同基因型和表型的胰腺癌细胞系（Panc-1、MIA PaCa-2和AsPC-1）形成球体。使用显微镜和流式细胞术（用7-AAD检测细胞活力，用膜联蛋白V-FITC/PI检测膜完整性）评估UA衍生物（C-2028、C-2045和C-2053）的作用。UAs改变了球体的形态并抑制了它们的生长。值得注意的是，Panc-1球体的完整性受到损害。7-AAD阳性细胞增加证实细胞活力降低，膜联蛋白V-FITC检测显示凋亡是主要的死亡途径。有趣的是，无论培养条件如何，特定的衍生物对给定的细胞系最具活性。这些结果证实UAs在三维培养中保持抗癌活性并诱导凋亡，不同细胞系的疗效不同。这突出了多种细胞模型在化合物评估中的价值，并支持UAs作为胰腺癌治疗的有前景的候选药物。
