奥沙利铂与β-胡萝卜素联合使用通过调节细胞周期、细胞凋亡和癌症干性来抑制结直肠癌。
Combination of oxaliplatin and β-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness .
作者信息
Lee Junghyeun, Heo Seung Chul, Kim Yuri
机构信息
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Korea.
Department of Surgery, Seoul National University-Seoul Metropolitan Government (SNU-SMG) Boramae Medical Center, Seoul 07061, Korea.
出版信息
Nutr Res Pract. 2024 Feb;18(1):62-77. doi: 10.4162/nrp.2024.18.1.62. Epub 2023 Dec 26.
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, G/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.
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原，已知具有抗氧化和抗癌作用。然而，OXA和BC的联合作用尚未得到研究。因此，本研究探讨了OXA和BC联合应用对CRC的抗癌作用及机制。
材料/方法：在本研究中，使用HCT116、HT29、OXA耐药细胞和人CRC类器官研究了OXA和BC联合应用对细胞活力、细胞周期阻滞和癌症干性的影响。
结果
OXA和BC联合应用可增强人CRC耐药细胞和CRC类器官中的细胞凋亡、G/M期细胞周期阻滞，并抑制癌细胞存活，而对正常类器官无毒性。联合使用OXA和BC可抑制癌症干细胞标志物的表达和自我复制能力。此外，这种联合治疗上调了细胞凋亡和干细胞相关的JAK/STAT信号通路。
结论
我们的结果表明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中的细胞周期、细胞凋亡和干性来实现的。
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