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顺铂对胰腺导管腺癌细胞系的不同细胞毒性作用。

Different Cytotoxic Effects of Cisplatin on Pancreatic Ductal Adenocarcinoma Cell Lines.

作者信息

Muscella Antonella, Cossa Luca G, Stefàno Erika, Rovito Gianluca, Benedetti Michele, Fanizzi Francesco P, Marsigliante Santo

机构信息

Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Università del Salento, Via Provinciale per Monteroni, 73100 Lecce, Italy.

出版信息

Int J Mol Sci. 2024 Dec 20;25(24):13662. doi: 10.3390/ijms252413662.

DOI:10.3390/ijms252413662
PMID:39769425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11727771/
Abstract

This study examined the response to cisplatin in BxPC-3, Mia-Paca-2, PANC-1, and YAPC pancreatic cancer lines with different genotypic and phenotypic characteristics, and the mechanisms associated with their resistance. BxPC-3 and MIA-PaCa-2 cell lines were the most sensitive to cisplatin, while YAPC and PANC-1 were more resistant. Consistently, in cisplatin-treated BxPC-3 cells, the cleavage patterns of pro-caspase-9, -7, -3, and PARP-1 demonstrated that they were more sensitive than YAPC cells. The autophagic pathway, promoting cisplatin resistance, was active in BxPC-3 cells, as demonstrated by the time-dependent conversion of LC3-I to LC3-II, whereas it was not activated in YAPC cells. In cisplatin-treated BxPC-3 cells, Bcl-2 decreased, while Beclin-1, Atg-3, and Atg-5 increased along with JNK1/2 phosphorylation. Basal levels of phosphorylated ERK1/2 in each cell line were positively correlated with cisplatin IC50 values, and cisplatin caused the activation of ERK1/2 in BxPC-3 and YAPC cells. Furthermore, ERK1/2 pharmacological inactivation increased cisplatin lethality in both BxPC-3 and YAPC cells, suggesting that p-ERK1/2 may be related to cisplatin resistance of PDAC cells. Different mechanisms and strategies are generally required to acquire drug resistance. Here, we partially explain the other response to cisplatin of BxPC-3 and YAPC cell lines by relating it to the role of ERK pathway.

摘要

本研究检测了具有不同基因型和表型特征的BxPC-3、Mia-Paca-2、PANC-1和YAPC胰腺癌细胞系对顺铂的反应及其耐药相关机制。BxPC-3和MIA-PaCa-2细胞系对顺铂最为敏感，而YAPC和PANC-1则更具耐药性。同样，在顺铂处理的BxPC-3细胞中，前半胱天冬酶-9、-7、-3和PARP-1的裂解模式表明它们比YAPC细胞更敏感。促进顺铂耐药的自噬途径在BxPC-3细胞中活跃，这通过LC3-I向LC3-II的时间依赖性转化得以证明，而在YAPC细胞中未被激活。在顺铂处理的BxPC-3细胞中，Bcl-2减少，而Beclin-1、Atg-3和Atg-5随着JNK1/2磷酸化而增加。各细胞系中磷酸化ERK1/2的基础水平与顺铂IC50值呈正相关，顺铂导致BxPC-3和YAPC细胞中ERK1/2的激活。此外，ERK1/2的药理学失活增加了BxPC-3和YAPC细胞对顺铂的致死率，表明p-ERK1/2可能与胰腺导管腺癌（PDAC）细胞的顺铂耐药有关。通常需要不同的机制和策略来获得耐药性。在此，我们通过将其与ERK途径的作用相关联，部分解释了BxPC-3和YAPC细胞系对顺铂的其他反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/291c/11727771/a7d25e3624e7/ijms-25-13662-g006.jpg
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