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Exploring the mechanism of resistance to vincristine in breast cancer cells using transcriptome sequencing technology

机译:利用转录组测序技术探索乳腺癌细胞对长春新碱耐药的机制

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摘要

Breast cancer has replaced lung cancer as the leading cancer globally, but various chemotherapy drugs for breast cancer are prone to resistance, especially in patients with distant metastases who are susceptible to multiple chemotherapy drug resistance often leading to treatment failure. Vincristine (VCR) is an alkaloid extracted from Catharanthus roseus , and is often used in combination with other chemotherapy drugs to treat various types of cancer, including breast cancer. Research on the development of resistance to VCR has been carried out using transcriptome sequencing technology. Firstly, gradient increase of VCR concentration was used to produce a VCR-resistant breast cancer cell line. Mechanistically, RNA was extracted from the VCR-resistant breast cancer cell line, and the transcriptome was sequenced. Further analysis showed changes in the expression levels of various genes in the aforementioned VCR-resistant breast cancer cell line. Meanwhile, the analysis of splicing events also indicated a change in variable splicing events. Further validation showed that the expression levels of multiple genes, including interleukin-1β, were altered in the VCR-resistant breast cancer cell line, and these gene expression changes were related to VCR resistance. The results of the present study provide a theoretical basis for exploring the mechanism of VCR resistance clinically.
机译:乳腺癌已取代肺癌成为全球主要癌症,但各种治疗乳腺癌的化疗药物容易产生耐药性,尤其是对多重化疗耐药易感的远处转移患者,往往导致治疗失败。长春新碱(VCR)是一种从蔷薇蔷薇中提取的生物碱,通常与其他化疗药物联合使用,以治疗各种类型的癌症,包括乳腺癌。使用转录组测序技术对VCR耐药性的发展进行了研究。首先,利用VCR浓度的梯度增加来生产耐VCR的乳腺癌细胞系。从机制上讲,从耐VCR的乳腺癌细胞系中提取RNA,并对转录组进行测序。进一步的分析显示,上述耐VCR乳腺癌细胞系中各种基因的表达水平发生了变化。同时,对剪接事件的分析也表明了可变剪接事件的变化。进一步验证表明,包括白细胞介素-1β在内的多个基因的表达水平在VCR耐药乳腺癌细胞系中发生了改变,这些基因表达变化与VCR耐药有关。本研究结果为临床上探讨VCR耐药机制提供了理论依据。

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