Department of Pharmacology, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200 Hebei Province, China.
Department of Nursing, Shijiazhuang Medical College, Shijiazhuang, 050500 Hebei Province, China.
Dis Markers. 2020 Sep 3;2020:5068067. doi: 10.1155/2020/5068067. eCollection 2020.
6,12-Diphenyl-3,9-diazatetraasterane-1, 5, 7, 11-tetracarboxylate (DDTC) has been synthesized by the photodimerization of 4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate. The potential of theercvantitumor activity and mechanism were investigated using MTT assay in human lung cancer cell line A549, ovarian cancer cell lines SKOV3 and A2780, breast cancer cell line MCF-7, gastric cancer cell line BGC-823, colon cancer cell line HT29, prostate cancer cell line DU145, and liver cancer cell line SMMC7721. The results show that DDTC can inhibit the growth of ovarian cancer SKOV3 and A2780 cells. The best IC value is approximately 5.29 ± 0.38 and 4.29 ± 0.39 M, respectively. DDTC induced the cell cycle arrest in the G2 phase by flow cytometric analysis. The migration and invasion of ovarian cancer SKOV3 and A2780 cells were inhibited by DDTC. DDTC could increase the expression protein level of E-cadherin in A2780 cells and ascend the expression protein and mRNA levels of E-cadherin in SKOV3 cells. DDTC could also decrease the protein and mRNA expression of EMT (epithelial-to-mesenchymal transition) markers of N-cadherin and Vimentin. mRNA and protein expression level of checkpoint kinase 1 (Chk1) were significantly increased and expressions of cyclin-dependent kinase (CDK1) and cell division cycle 25a (Cdc25a) were decreased in the SKOV3 and A2780 cell lines. Moreover, DDTC induced apoptosis by the cleavage and activation of caspase 3 and caspase 9.
6,12-二苯基-3,9-二氮杂四环[5.5.0.02,6.03,10.07,12]十三烷-1,5,7,11-四羧酸酯（DDTC）是通过 4-苯基-1,4-二氢吡啶-3,5-二羧酸酯的光二聚化合成的。使用 MTT 法在人肺癌细胞系 A549、卵巢癌细胞系 SKOV3 和 A2780、乳腺癌细胞系 MCF-7、胃癌细胞系 BGC-823、结肠癌细胞系 HT29、前列腺癌细胞系 DU145 和肝癌细胞系 SMMC7721 中研究了其潜在的抗肿瘤活性和机制。结果表明，DDTC 能抑制卵巢癌细胞 SKOV3 和 A2780 的生长。最佳 IC 值分别约为 5.29±0.38 和 4.29±0.39μM。通过流式细胞术分析，DDTC 诱导细胞周期阻滞在 G2 期。DDTC 抑制卵巢癌细胞 SKOV3 和 A2780 的迁移和侵袭。DDTC 能增加 A2780 细胞中 E-钙黏蛋白的表达蛋白水平，并使 SKOV3 细胞中 E-钙黏蛋白的表达蛋白和 mRNA 水平升高。DDTC 还能降低 EMT（上皮-间充质转化）标志物 N-钙黏蛋白和波形蛋白的蛋白和 mRNA 表达。SKOV3 和 A2780 细胞系中检查点激酶 1（Chk1）的 mRNA 和蛋白表达水平显著增加，细胞周期蛋白依赖性激酶（CDK1）和细胞分裂周期 25a（Cdc25a）的表达减少。此外，DDTC 通过切割和激活半胱天冬酶 3 和半胱天冬酶 9 诱导细胞凋亡。
