Abstract—

Osteosarcoma is the most prevalent bone malignant tumor with a high mortality rate among children and adolescents (10–19 years of age). The Aryl Hydrocarbon Receptor (AHR) is a ligand-dependent transcription factor associated with xenobiotic detoxification and carcinogenesis. It is known that some AHR ligands are included in the composition of drugs used in cancer therapy. However, there are few works devoted to the study of their effect on osteosarcoma cells. In this work, three primary cell cultures were obtained from biopsy material of malignant bone tumors of human osteosarcoma. AHR protein levels were high in all primary osteosarcoma cell cultures. The functional activity of AHR in osteosarcoma cells was estimated by induction of its target genes by known exogenous ligands: indirubin and indole-3-carbinol. The genes of cytochrome P450 1 family CYP1 were analyzed as AHR target genes: CYP1A1, CYP1A2, and CYP1B1. It was shown that the aryl hydrocarbon receptor is functionally active in all cultures, but the target genes were induced differently by ligand treatment within the same cell culture.

中文翻译：

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芳基烃受体在人骨肉瘤细胞培养中的功能活性

摘要-

骨肉瘤是最普遍的骨恶性肿瘤，在儿童和青少年（10至19岁）中死亡率很高。芳香烃受体（AHR）是与异种毒素解毒和癌变有关的依赖配体的转录因子。已知一些AHR配体包括在用于癌症治疗的药物组合物中。但是，很少有研究致力于研究其对骨肉瘤细胞的作用。在这项工作中，从人骨肉瘤恶性骨肿瘤的活检材料中获得了三种原代细胞培养物。在所有原发性骨肉瘤细胞培养物中，AHR蛋白水平较高。通过已知的外源配体：靛玉红和吲哚-3-甲醇诱导AHR的靶基因，可以评估AHR在骨肉瘤细胞中的功能活性。分析细胞色素P450 1家族CYP1的基因作为AHR靶基因：CYP1A1，CYP1A2和CYP1B1。结果表明，芳烃受体在所有培养物中均具有功能活性，但是在同一细胞培养物中，通过配体处理，靶基因的诱导方式有所不同。