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瘦素对MDA-MB-231三阴性乳腺癌细胞多西他赛敏感性影响的初步机制探索

A preliminary mechanistic exploration of the effect of leptin on the docetaxel sensitivity of MDA‑MB‑231 triple‑negative breast cancer cells.

作者信息

Gao Simeng, Ding Sijuan, Tang Zhaohui

机构信息

Department of Oncology, The Central Hospital of Yongzhou, Yongzhou, Hunan 425000, P.R. China.

出版信息

Mol Clin Oncol. 2024 Feb 1;20(3):24. doi: 10.3892/mco.2024.2722. eCollection 2024 Mar.

Abstract

Breast cancer is a common tumor encountered in women, and triple-negative breast cancer (TNBC) has an extremely poor prognosis. The effect of leptin on the docetaxel sensitivity of MDA-MB-231 TNBC cells has not been investigated. The present study aimed to clarify the effect of leptin and M2 tumor-associated macrophages (TAMs) on the chemosensitivity of TNBC cell lines and its possible mechanisms. In the present study, the apoptosis of the MDA-MB-231 cell line was detected at 0, 24, 48 and 72 h using a Cell Counting Kit-8 assay to determine the appropriate concentration of docetaxel as well as the IC value. After determining the effect of leptin on TAMs, the conditioned medium with an appropriate concentration of docetaxel was collected to treat the breast cancer cells, and flow cytometry was used to detect the cell cycle distribution and apoptosis in different treatment groups. Interleukin 8 (IL-8) expression was detected using ELISA and western blot assay. The IL-8 antibody was used to neutralize IL-8, and invasion and scratch assays were used to detect changes in invasion and migration of breast cancer cells. Statistical analysis was performed using GraphPad Prism 9.0 and SPSS 22.0. It was revealed that the apoptotic rate of MDA-MB-231 cells in the leptin-treated TAMs group was lower than that in other groups. The expression of IL-8 was notably elevated in the group treated with leptin-activated TAMs compared with that in the other groups. The neutralization of IL-8 resulted in a significant reduction in the invasive migration of MDA-MB-231 cells compared with that in the non-neutralized group.

摘要

乳腺癌是女性中常见的肿瘤,而三阴性乳腺癌(TNBC)的预后极差。尚未研究瘦素对MDA-MB-231 TNBC细胞多西他赛敏感性的影响。本研究旨在阐明瘦素和M2肿瘤相关巨噬细胞(TAM)对TNBC细胞系化疗敏感性的影响及其可能机制。在本研究中,使用细胞计数试剂盒-8检测在0、24、48和72小时时MDA-MB-231细胞系的凋亡情况,以确定多西他赛的合适浓度以及IC值。在确定瘦素对TAM的影响后,收集含有合适浓度多西他赛的条件培养基来处理乳腺癌细胞,并使用流式细胞术检测不同处理组的细胞周期分布和凋亡情况。使用ELISA和蛋白质免疫印迹法检测白细胞介素8(IL-8)的表达。使用IL-8抗体中和IL-8,并使用侵袭和划痕试验检测乳腺癌细胞侵袭和迁移的变化。使用GraphPad Prism 9.0和SPSS 22.0进行统计分析。结果显示,瘦素处理的TAM组中MDA-MB-231细胞的凋亡率低于其他组。与其他组相比,瘦素激活的TAM处理组中IL-8的表达显著升高。与未中和组相比,IL-8的中和导致MDA-MB-231细胞的侵袭性迁移显著降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacb/10895386/780203827be5/mco-20-03-02722-g00.jpg

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