通过促进细胞凋亡和抑制细胞周期,将异丙酚重新用于乳腺癌治疗。

IF 3.8 3区 医学 Q2 ONCOLOGY Oncology reports Pub Date : 2024-11-01 Epub Date: 2024-10-04 DOI:10.3892/or.2024.8814
Peng Sun, Hanqing Huang, Jian-Chao Ma, Binyang Feng, Yiqing Zhang, Genggeng Qin, Weian Zeng, Zhong-Kai Cui
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引用次数: 0

摘要

乳腺癌是全球女性中发病率最高的癌症,其特点是死亡率高且容易转移。虽然手术是乳腺癌的标准治疗方法,但目前仍没有有效的方法来抑制肿瘤转移和改善乳腺癌患者术后的预后。异丙酚是手术中最广泛使用的静脉麻醉剂之一,它与乳腺癌患者术后生存率的改善呈正相关。然而,其潜在的分子机制仍有待阐明。本研究发现,暴露于异丙酚的三阴性乳腺癌细胞 MDA-MB-231 和 4T1 的细胞活力显著下降。值得注意的是,在相同条件下,异丙酚对 HUVEC 的细胞毒性作用很小。此外,异丙酚还能明显抑制 MDA-MB-231 和 4T1 细胞的迁移和侵袭能力。异丙酚通过上调 Bax 和裂解的 caspase 3 促进了 4T1 细胞的凋亡,同时下调了 B 细胞淋巴瘤-extra large。同时,异丙酚通过下调细胞周期蛋白 E2 和磷酸化细胞分裂周期 6,诱导 4T1 细胞的细胞周期停滞。此外,异丙酚在 4T1 乳腺癌异体移植小鼠模型中表现出卓越的抗癌功效。本研究揭示了异丙酚作为一种古老药物在乳腺癌治疗中的新用途潜力。
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Repurposing propofol for breast cancer therapy through promoting apoptosis and arresting cell cycle.

Breast cancer is the most prevalent cancer among women worldwide, characterized by a high mortality rate and propensity for metastasis. Although surgery is the standard treatment for breast cancer, there is still no effective method to inhibit tumor metastasis and improve the prognosis of patients with breast cancer after surgery. Propofol, one of the most widely used intravenous anesthetics in surgery, has exhibited a positive association with improved survival outcomes in patients with breast cancer post‑surgery. However, the underlying molecular mechanism remains to be elucidated. The present study revealed that triple negative breast cancer cells, MDA‑MB‑231 and 4T1, exposed to propofol exhibited a significant decrease in cell viability. Notably, propofol exhibited minimal cytotoxic effects on HUVECs under the same conditions. Furthermore, propofol significantly inhibited the migration and invasion ability of MDA‑MB‑231 and 4T1 cells. Propofol promoted apoptosis in 4T1 cells through upregulation of Bax and cleaved caspase 3, while downregulating B‑cell lymphoma‑extra large. Concomitantly, propofol induced cell cycle arrest of 4T1 cells by downregulating cyclin E2 and phosphorylated cell division cycle 6. Furthermore, propofol exhibited excellent anticancer efficacy in a 4T1 breast cancer allograft mouse model. The present study sheds light on the potential of propofol as an old medicine with a novel use for breast cancer treatment.

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来源期刊
Oncology reports
Oncology reports 医学-肿瘤学
CiteScore
8.50
自引率
2.40%
发文量
187
审稿时长
3 months
期刊介绍: Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
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