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紫草素通过 p38 依赖性细胞凋亡诱导抗肿瘤作用。

Shikonin induces an anti‑tumor effect on murine mammary cancer via p38‑dependent apoptosis.

机构信息

Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930‑0194, Japan.

Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930‑0194, Japan.

出版信息

Oncol Rep. 2019 Mar;41(3):2020-2026. doi: 10.3892/or.2019.6966. Epub 2019 Jan 11.

DOI:10.3892/or.2019.6966
PMID:30664166
Abstract

Breast cancer is the most common malignancy in women. Apoptosis is important for tumor suppression and may delay cancer progression. It was found that shikonin induced apoptosis in 4T1 murine mammary cancer cells and MDA‑MB‑231 human breast cancer cells in vitro. Total p38 and c‑Jun N‑terminal kinase (JNK) levels were maintained in 4T1 cells, and p38 phosphorylation, but not JNK phosphorylation, was significantly increased. Caspase‑3/7 activity was detected, which suggested that the p38 pathway, but not the JNK signaling pathway, induced apoptosis in 4T1 cells. The anti‑tumor effects of shikonin on orthotopic mouse models were also examined. On day 7 after inoculation of 4T1 cells into mice, tumor volumes in the shikonin‑treated and the control groups began to differ. On day 13, tumors were weighed, and shikonin was revealed to suppress tumor growth in the orthotopic 4T1 model in vivo. In conclusion, shikonin is a potential anti‑tumor drug for breast cancer.

摘要

乳腺癌是女性最常见的恶性肿瘤。细胞凋亡对于肿瘤抑制至关重要,可能会延缓癌症的进展。研究发现,紫草素可在体外诱导 4T1 鼠乳腺癌细胞和 MDA-MB-231 人乳腺癌细胞发生凋亡。4T1 细胞中总 p38 和 c-Jun N-末端激酶(JNK)水平保持不变,而 p38 磷酸化而非 JNK 磷酸化显著增加。检测到半胱天冬酶-3/7 活性,表明 p38 通路而非 JNK 信号通路诱导了 4T1 细胞的凋亡。还研究了紫草素对原位小鼠模型的抗肿瘤作用。在将 4T1 细胞接种到小鼠体内的第 7 天,紫草素处理组和对照组的肿瘤体积开始出现差异。在第 13 天,对肿瘤进行称重,结果显示紫草素可抑制体内原位 4T1 模型的肿瘤生长。综上所述,紫草素是一种有潜力的乳腺癌抗肿瘤药物。

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