Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2022 May 18;23(10):5645. doi: 10.3390/ijms23105645.
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide. Current therapeutic strategies mainly involve surgery and chemoradiotherapy; however, novel antitumor compounds are needed to avoid drug resistance in CRC, as well as the severe side effects of current treatments. In this study, we investigated the anticancer effects and underlying mechanisms of Arylquin 1 in CRC. The MTT assay was used to detect the viability of SW620 and HCT116 cancer cells treated with Arylquin 1 in a dose-dependent manner in vitro. Further, wound-healing and transwell migration assays were used to evaluate the migration and invasion abilities of cultured cells, and Annexin V was used to detect apoptotic cells. Additionally, Western blot was used to identify the expression levels of N-cadherin, caspase-3, cyclin D1, p-extracellular signal-regulated kinase (ERK), p-c-JUN N-terminal kinase (JNK), and phospho-p38, related to key signaling proteins, after administration of Arylquin 1. Xenograft experiments further confirmed the effects of Arylquin 1 on CRC cells in vivo. Arylquin 1 exhibited a dose-dependent reduction in cell viability in cultured CRC cells. It also inhibited cell proliferation, migration, and invasion, and induced apoptosis. Mechanistic analysis demonstrated that Arylquin 1 increased phosphorylation levels of ERK, JNK, and p38. In a mouse xenograft model, Arylquin 1 treatment diminished the growth of colon tumors after injection of cultured cancer cells. Arylquin 1 may have potential anticancer effects and translational significance in the treatment of CRC.
结直肠癌（CRC）是全球最常见的胃肠道癌症之一。目前的治疗策略主要包括手术和放化疗；然而，需要新型的抗肿瘤化合物来避免 CRC 中的药物耐药性，以及当前治疗方法的严重副作用。在本研究中，我们研究了 Arylquin 1 在 CRC 中的抗癌作用和潜在机制。MTT 法检测了 Arylquin 1 以剂量依赖方式处理体外 SW620 和 HCT116 癌细胞后的活力。进一步，划痕愈合和 Transwell 迁移实验用于评估培养细胞的迁移和侵袭能力，并用 Annexin V 检测凋亡细胞。此外，Western blot 用于鉴定给药后与关键信号蛋白相关的 N-钙粘蛋白、半胱天冬酶-3、细胞周期蛋白 D1、p-细胞外信号调节激酶（ERK）、p-JUN N 末端激酶（JNK）和磷酸化 p38 的表达水平。异种移植实验进一步证实了 Arylquin 1 对体内 CRC 细胞的作用。Arylquin 1 对培养的 CRC 细胞表现出剂量依赖性的细胞活力降低。它还抑制细胞增殖、迁移和侵袭，并诱导细胞凋亡。机制分析表明 Arylquin 1 增加了 ERK、JNK 和 p38 的磷酸化水平。在小鼠异种移植模型中，Arylquin 1 治疗在注射培养的癌细胞后减轻了结肠肿瘤的生长。Arylquin 1 可能在 CRC 治疗中具有潜在的抗癌作用和转化意义。
