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维生素 C 通过细胞氧化剂功能相关钙黏蛋白分子增强奥沙利铂对 HCT-116 结直肠癌细胞生长和进展的抑制作用。

Vitamin C Improves the Inhibitory Effects of Oxaliplatin on HCT-116 Colorectal Cancer Growth and Progression Through Cellular Oxidant Function-associated Cadherin Molecules.

机构信息

Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand.

出版信息

Anticancer Res. 2023 Oct;43(10):4461-4472. doi: 10.21873/anticanres.16641.

DOI:10.21873/anticanres.16641
PMID:37772573
Abstract

BACKGROUND/AIM: Colorectal cancer (CRC) is strongly associated with altered cadherin adhesion molecules. Oxaliplatin is a standard treatment for CRC, yet high-doses have concerning side effects. In this study, the effects of oxaliplatin and the combination of oxaliplatin with vitamin C on HCT-116 CRC cell migration and invasion were studied through the roles of cellular oxidative stress associated with cadherin molecules.

MATERIALS AND METHODS

The cellular assays used in this research were MTT, DCFH-DA, immunofluorescence, and western blotting. Cancer progression was examined using wound healing and Boyden chamber techniques.

RESULTS

The results indicate that hydrogen peroxide-induced cellular oxidative stress induced cancer cell migration and invasion. The combined treatment of oxaliplatin with a pro-oxidant concentration of vitamin C resulted in higher toxicity than treatment with oxaliplatin alone. However, treatment with the combination of oxaliplatin and antioxidant concentrations of vitamin C suppressed cancer migration and invasion. Furthermore, the combination treatment increased E-cadherin expression, whereas decreased that of N-cadherin.

CONCLUSION

Treatment with the combination of oxaliplatin with vitamin C can inhibit CRC cell growth and decrease cancer cell migration and invasion, via oxidative stress and cadherins.

摘要

背景/目的:结直肠癌(CRC)与细胞黏附分子中 cadherin 的改变密切相关。奥沙利铂是 CRC 的标准治疗方法,但高剂量有令人担忧的副作用。在这项研究中,通过与 cadherin 分子相关的细胞氧化应激作用,研究了奥沙利铂和奥沙利铂与维生素 C 联合治疗对 HCT-116 CRC 细胞迁移和侵袭的影响。

材料和方法

本研究中使用的细胞检测方法包括 MTT、DCFH-DA、免疫荧光和 Western blot。使用划痕愈合和 Boyden 室技术检测癌症进展。

结果

结果表明,过氧化氢诱导的细胞氧化应激诱导癌细胞迁移和侵袭。奥沙利铂与促氧化剂浓度的维生素 C 联合治疗比单独使用奥沙利铂的毒性更高。然而,奥沙利铂与抗氧化剂浓度的维生素 C 的联合治疗抑制了癌症的迁移和侵袭。此外,联合治疗增加了 E-cadherin 的表达,而降低了 N-cadherin 的表达。

结论

奥沙利铂与维生素 C 的联合治疗可通过氧化应激和 cadherin 抑制 CRC 细胞生长并降低癌细胞迁移和侵袭。

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