“联合使用伊马替尼、虾青素和藏红花苷可以有效改善伊马替尼耐药性慢性髓系白血病细胞的抗氧化状态、炎症和细胞死亡进展”。

"Combination treatments of imatinib with astaxanthin and crocin efficiently ameliorate antioxidant status, inflammation and cell death progression in imatinib-resistant chronic myeloid leukemia cells".

机构信息

Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.

Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

Mol Biol Rep. 2024 Jan 16;51(1):108. doi: 10.1007/s11033-023-09135-4.

DOI:10.1007/s11033-023-09135-4

PMID:38227060

Abstract

BACKGROUND

Imatinib resistance remains a major obstacle in the treatment of chronic myelogenous leukemia (CML). Crocin (CRC) and astaxanthin (ATX) are phytochemicals with anti-cancer properties.

AIMS

This study aimed to explore the effects of combination treatment of Imatinib with CRC and ATX on Imatinib-resistant K562 (IR-K562) cells.

METHODS AND RESULTS

After the establishment of IR-K562 cells, growth inhibitory activity was determined by the MTT assay. To test the regeneration potential, a colony formation assay was performed. Cell cycle analyses were examined by flow cytometry. Cell injury was evaluated by lactate dehydrogenase (LDH) leakage. Real-time PCR was applied to assess the expression of IL6, TNF-α, STAT3, BAD, CASP3, TP53, and Bcl-2 genes. Caspase-3 activity was determined by a colorimetric assay. Antioxidant activity was measured using a diphenylpicrylhydrazyl (DPPH) assay. After 48 h of treatment, ATX (IC = 30µM) and CRC (IC = 190µM) significantly inhibited cell proliferation and colony formation ability, induced G1 cell cycle arrest and cell injury, upregulated the expression of apoptosis-associated genes, and downregulated the expression of anti-apoptotic and inflammatory genes. The combination of IM with ATX and/or CRC synergistically reduced cell viability (combination index [CI] < 1).

CONCLUSION

Our data suggest that IM shows better therapeutic efficacy at lower doses when combined with ATX and/or CRC.

摘要

背景

伊马替尼耐药仍然是慢性髓性白血病（CML）治疗的主要障碍。藏红花酸（CRC）和虾青素（ATX）是具有抗癌特性的植物化学物质。

目的

本研究旨在探讨伊马替尼与 CRC 和 ATX 联合治疗伊马替尼耐药 K562（IR-K562）细胞的效果。

方法和结果

在建立 IR-K562 细胞后，通过 MTT 测定法测定生长抑制活性。为了测试再生潜力，进行了集落形成测定。通过流式细胞术检查细胞周期分析。通过乳酸脱氢酶（LDH）渗漏评估细胞损伤。实时 PCR 用于评估 IL6、TNF-α、STAT3、BAD、CASP3、TP53 和 Bcl-2 基因的表达。通过比色法测定 caspase-3 活性。使用二苯基苦基肼（DPPH）测定法测量抗氧化活性。治疗 48 小时后，ATX（IC = 30µM）和 CRC（IC = 190µM）显著抑制细胞增殖和集落形成能力，诱导 G1 细胞周期停滞和细胞损伤，上调凋亡相关基因的表达，并下调抗凋亡和炎症基因的表达。IM 与 ATX 和/或 CRC 联合使用可协同降低细胞活力（组合指数 [CI] < 1）。