Karaselek Mehmet Ali, Kuccukturk Serkan, Duran Tugce, Kursunlu Ahmed Nuri, Ozmen Mustafa, Bozdag Ceren, Alkan Selman, Varman Alper, Yildirim Mehmet Aykut, Kucukkartallar Tevfik, Vatansev Celalettin
Meram Medicine Faculty, Department of Internal Medicine, Necmettin Erbakan University, Konya, 42080, Türkiye.
Medicine Faculty, Department of Medical Biology, Karamanoglu Mehmetbey University, Karaman, 70100, Türkiye.
Invest New Drugs. 2023 Apr;41(2):202-209. doi: 10.1007/s10637-023-01343-w. Epub 2023 Mar 11.
This study aimed to evaluate the possible anticancer effects of two different pillar[5]arene derivatives (5Q-[P5] and 10Q-P[5]) on two different pancreatic cancer cell lines in vitro. For this purpose, changes in the expression of major genes that play a role in apoptosis and caspase pathways were investigated. Panc-1 and BxPC-3 cell lines were used in the study and the cytotoxic dose of pillar[5]arenes was determined by the MTT method. Changes in gene expression after pillar[5]arenes treatment were evaluated by real-time polymerase chain reaction (qPCR). Apoptosis was studied by flow cytometry. As a result of analysis, it was determined that proapoptotic genes and genes involved in major caspase activation were upregulated and antiapoptotic genes were down-regulated in Panc-1 cell line treated with pillar[5]arenes. Flow cytometric apoptosis analysis also showed an increased apoptosis rate in this cell line. On the contrary, although MTT analysis showed cytotoxic effect in BxPC-3 cell line treated with two pillar[5]arene derivatives, the apoptosis pathway was not active. This suggested that it may activate different death pathways for BxPC-3 cell line. Thus, it was first determined that the pillar[5]arene derivatives reduced cancer cell proliferation on pancreatic cancer cells.
本研究旨在评估两种不同的柱[5]芳烃衍生物(5Q-[P5]和10Q-P[5])对两种不同胰腺癌细胞系的体外抗癌作用。为此,研究了在细胞凋亡和半胱天冬酶途径中起作用的主要基因表达的变化。本研究使用了Panc-1和BxPC-3细胞系,并通过MTT法确定了柱[5]芳烃的细胞毒性剂量。通过实时聚合酶链反应(qPCR)评估柱[5]芳烃处理后基因表达的变化。通过流式细胞术研究细胞凋亡。分析结果表明,在用柱[5]芳烃处理的Panc-1细胞系中,促凋亡基因和参与主要半胱天冬酶激活的基因上调,抗凋亡基因下调。流式细胞术凋亡分析也显示该细胞系的凋亡率增加。相反,尽管MTT分析显示两种柱[5]芳烃衍生物处理的BxPC-3细胞系具有细胞毒性作用,但凋亡途径并不活跃。这表明它可能激活BxPC-3细胞系的不同死亡途径。因此,首先确定柱[5]芳烃衍生物可降低胰腺癌细胞的增殖。