Department of Urology Surgery, Baoding No. 1 Hospital, Baoding, China.
Department of Urology Surgery, Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820926591. doi: 10.1177/1533033820926591.
Desloratadine, a potent antagonist for human histamine H1 receptor, has been revealed to exhibit antihistaminic activity and anti-inflammatory activity. However, it is not yet known whether desloratadine has any effect on the biological behaviors of tumor cells. In this study, we aimed to investigate the effects of desloratadine on cell growth and invasion in bladder cancer EJ and SW780 cells . We observed that desloratadine inhibited cell viability of EJ and SW780 cells in a dose- and time-dependent manner. Desloratadine treatment was also revealed to suppress colony-formation ability and induce cell cycle arrest at G1 phase in EJ cells. Desloratadine promoted cell apoptosis via modulating the expression of Bcl-2, Bax, cleaved caspase 3, and cleaved caspase 9 in EJ and SW780 cells. Western blot resulted showed that desloratadine also impaired the expression of autophagy-related proteins, such as Beclin 1, P62, and LC3I/II in EJ and SW780 cells; while autophagy inhibitor LY294002 reversed the effects of desloratadine on these proteins. Moreover, desloratadine remarkably attenuated cell migration and invasion. Furthermore, we illustrated that desloratadine downregulated the expression of N-cadherin, Vimentin, Snail1, and Snail2, while upregulated the expression of E-cadherin in EJ and SW780 cells . The level of interleukin 6 was reduced in desloratadine-treated cells, while upregulation of interleukin 6 significantly abolished the anticancer activity of desloratadine in cell invasion and Bcl-2, Bax, Beclin1, LC3-I/II, N-cadherin, and E-cadherin expression in EJ cells. Taken together, our data suggest a potential anticancer activity of desloratadine on cell growth and invasion for bladder cancer, which may be mediated by diminishing the epithelial-to-mesenchymal transition and interleukin 6.
地氯雷他定是一种强效的人组胺 H1 受体拮抗剂，已被证实具有抗组胺和抗炎活性。然而，目前尚不清楚地氯雷他定是否对肿瘤细胞的生物学行为有影响。在这项研究中，我们旨在探讨地氯雷他定对膀胱癌 EJ 和 SW780 细胞生长和侵袭的影响。我们观察到地氯雷他定呈剂量和时间依赖性地抑制 EJ 和 SW780 细胞的活力。地氯雷他定处理还抑制了 EJ 细胞的集落形成能力，并诱导细胞周期停滞在 G1 期。地氯雷他定通过调节 EJ 和 SW780 细胞中 Bcl-2、Bax、cleaved caspase 3 和 cleaved caspase 9 的表达，促进细胞凋亡。Western blot 结果显示，地氯雷他定还损害了 EJ 和 SW780 细胞中自噬相关蛋白的表达，如 Beclin 1、P62 和 LC3I/II；而自噬抑制剂 LY294002 逆转了地氯雷他定对这些蛋白的影响。此外，地氯雷他定显著抑制细胞迁移和侵袭。此外，我们表明地氯雷他定下调了 EJ 和 SW780 细胞中 N-钙粘蛋白、波形蛋白、Snail1 和 Snail2 的表达，而上调了 E-钙粘蛋白的表达。地氯雷他定处理的细胞中白细胞介素 6 的水平降低，而上调白细胞介素 6 显著消除了地氯雷他定在细胞侵袭和 Bcl-2、Bax、Beclin1、LC3-I/II、N-钙粘蛋白和 E-钙粘蛋白表达方面对 EJ 细胞的抗癌活性。综上所述，我们的数据表明地氯雷他定对膀胱癌的细胞生长和侵袭具有潜在的抗癌活性，这可能是通过减少上皮-间充质转化和白细胞介素 6 来介导的。
