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6,12-Diphenyl-3, 9-diazatetraasterane-1, 5, 7, 11-tetracarboxylate Inhibits Proliferation, Migration and Promotes Apoptosis in Ovarian Cancer Cells.
Disease Markers ( IF 3.464 ) Pub Date : 2020-09-03 , DOI: 10.1155/2020/5068067
Pingping Chen 1 , Huibing Wang 1 , Meng Li 1 , Linqi Yang 1 , Feifei Mou 2 , Bhupinder Singh 3 , Jing-Yu He 4 , Wei Zhang 1
Affiliation  

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 in vitro 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 IC50 value is approximately and μM, 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.

中文翻译:

6,12-Dipheny-3, 9-diazatetraasterane-1, 5, 7, 11-tetracarboxylate 抑制卵巢癌细胞的增殖、迁移并促进细胞凋亡。

通过 4-苯基-1,4-二氢吡啶-3,5-二羧酸酯的光二聚反应合成了 6,12-二苯基-3,9-二氮杂四甾烷-1,5,7,11-四羧酸酯 (DDTC)。采用MTT法研究人肺癌细胞系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、结肠癌细胞系的体外抗肿瘤活性和机制。HT29、前列腺癌细胞系DU145和肝癌细胞系SMMC7721。结果表明,DDTC能够抑制卵巢癌SKOV3和A2780细胞的生长。最佳 IC 50值约为分别为μM。通过流式细胞术分析,DDTC 诱导细胞周期停滞在 G2 期。DDTC抑制卵巢癌SKOV3和A2780细胞的迁移和侵袭。DDTC可以增加A2780细胞中E-cadherin蛋白的表达水平,并上调SKOV3细胞中E-cadherin蛋白和mRNA的表达水平。DDTC 还可以降低 N-钙粘蛋白和波形蛋白的 EMT(上皮间质转化)标记物的蛋白质和 mRNA 表达。在 SKOV3 和 A2780 细胞系中,检查点激酶 1 (Chk1) 的 mRNA 和蛋白表达水平显着升高,而细胞周期蛋白依赖性激酶 (CDK1) 和细胞分裂周期 25a (Cdc25a) 的表达水平降低。此外,DDTC 通过裂解和激活 caspase 3 和 caspase 9 诱导细胞凋亡。
更新日期:2020-09-03
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