苯并噻嗪和三氟拉嗪对 POPDC1 表达的调控抑制结肠癌的生长和迁移。
Modulation of POPDC1 Expression by Phenothiazine and Trifluoperazine Suppress Colon Cancer Growth and Migration.
机构信息
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia.
Department of Medical Laboratory Science, Cihan University, Erbil, Iraq.
出版信息
Asian Pac J Cancer Prev. 2022 Aug 1;23(8):2863-2871. doi: 10.31557/APJCP.2022.23.8.2863.
OBJECTIVE
The aim of this study was to investigate the effects of CaM antagonist, PTZ, and TFP on cell proliferation and migration of colon cancer cells and its impact on POPDC protein expression.
METHODS
The 50% inhibitory concentration (IC50) of PTZ and TFP in SW1116, SW480, HCT-15, and COLO205 colon cancer cell lines are measured using MTT. Western blot and immunocytochemistry were used to determine the expression of PCNA, cyclin D1 (CD1), and POPDC proteins. Cell migration was observed using a scratch wound-healing assay.
RESULTS
Treatment with PTZ and TFP inhibited colon cancer cells growth in a dose-dependent manner. PTZ and TFP significantly inhibited the activation of proliferation markers, PCNA and CD1, and the migration of colon cancer cells. Furthermore, POPDC protein was significantly suppressed in all cell types of colon cancer, particularly in SW480. Finally, the CaM antagonist upregulates the POPDC1 expression in colon cancer cells.
CONCLUSION
These findings suggest that CaM antagonists suppress colon cancer cells proliferation via downregulation of CD1 and PCNA. In addition, POPDC protein could be used as a biomarker in colon cancer, and CaM antagonist could be used to regulate POPDC1 expression. This study suggests that targeting POPDC1 with CaM inhibition could be a potential therapeutic strategy for colon cancer treatment.
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目的
本研究旨在探讨钙调蛋白拮抗剂、PTZ 和 TFP 对结肠癌细胞增殖和迁移的影响及其对 POPDC 蛋白表达的影响。
方法：采用 MTT 法测定 PTZ 和 TFP 在 SW1116、SW480、HCT-15 和 COLO205 结肠癌细胞系中的 50%抑制浓度（IC50）。采用 Western blot 和免疫细胞化学法检测 PCNA、细胞周期蛋白 D1（CD1）和 POPDC 蛋白的表达。采用划痕愈合试验观察细胞迁移。
结果：PTZ 和 TFP 处理呈剂量依赖性抑制结肠癌细胞生长。PTZ 和 TFP 显著抑制增殖标志物 PCNA 和 CD1 的激活以及结肠癌细胞的迁移。此外，POPDC 蛋白在所有结肠癌细胞类型中均明显受到抑制，在 SW480 中尤为明显。最后，钙调蛋白拮抗剂上调结肠癌细胞中 POPDC1 的表达。
结论：这些发现表明钙调蛋白拮抗剂通过下调 CD1 和 PCNA 抑制结肠癌细胞增殖。此外，POPDC 蛋白可作为结肠癌细胞的生物标志物，钙调蛋白拮抗剂可用于调节 POPDC1 的表达。本研究表明，钙调蛋白抑制靶向 POPDC1 可能是治疗结肠癌的潜在治疗策略。
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