Combination of oxaliplatin and β-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness in vitro.

IF 2 4区医学 Q3 NUTRITION & DIETETICS Nutrition Research and Practice Pub Date : 2024-02-01 Epub Date: 2023-12-26 DOI:10.4162/nrp.2024.18.1.62

Junghyeun Lee, Seung Chul Heo, Yuri Kim

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Abstract

Background/objectives: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. β-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC.

Materials/methods: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids.

Results: The combination of OXA and BC enhanced apoptosis, G₂/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway.

Conclusions: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

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奥沙利铂与β-胡萝卜素联合使用可通过调节体外细胞周期、细胞凋亡和癌症干细胞抑制结直肠癌。

背景/目的：结直肠癌（CRC）是全球第三大常见癌症，复发率很高。奥沙利铂（OXA）耐药性是阻碍 CRC 治疗的主要原因之一。β-胡萝卜素（BC）是一种维生素 A，具有抗氧化和抗癌作用。然而，尚未研究过 OXA 和 BC 的联合作用。因此，本研究探讨了 OXA 和 BC 联合作用对 CRC 的抗癌作用及其机制：本研究使用HCT116、HT29、OXA耐药细胞和人CRC器官组织研究了OXA和BC联用对细胞活力、细胞周期停滞和癌症干性的影响：结果：OXA和BC联合使用可增强人CRC耐药细胞和CRC器官组织的细胞凋亡、G2/M期细胞周期停滞，并抑制癌细胞存活，而对正常器官组织无毒性。OXA和BC联合治疗可抑制癌症干细胞标记物的表达和自我复制能力。此外，这种联合治疗还能上调细胞凋亡和干细胞相关的JAK/STAT信号通路：我们的研究结果表明，BC在降低对OXA的耐药性方面具有新的潜在作用，从而增强了OXA的抗癌效果。这种增强是通过调节 CRC 的细胞周期、凋亡和干细胞来实现的。

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来源期刊

Nutrition Research and Practice NUTRITION & DIETETICS-

CiteScore

3.50

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： Nutrition Research and Practice (NRP) is an official journal, jointly published by the Korean Nutrition Society and the Korean Society of Community Nutrition since 2007. The journal had been published quarterly at the initial stage and has been published bimonthly since 2010. NRP aims to stimulate research and practice across diverse areas of human nutrition. The Journal publishes peer-reviewed original manuscripts on nutrition biochemistry and metabolism, community nutrition, nutrition and disease management, nutritional epidemiology, nutrition education, foodservice management in the following categories: Original Research Articles, Notes, Communications, and Reviews. Reviews will be received by the invitation of the editors only. Statements made and opinions expressed in the manuscripts published in this Journal represent the views of authors and do not necessarily reflect the opinion of the Societies.