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吗啡可通过阻滞细胞周期和诱导凋亡来抑制乳腺癌MCF-7细胞的生长。

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis.

作者信息

Chen Yanhua, Qin Yi, Li Li, Chen Jing, Zhang Xu, Xie Yubo

机构信息

Department of Anesthesiology in Cardiovascular Institute, The First Affiliated Hospital of Guangxi Medical University.

Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University.

出版信息

Biol Pharm Bull. 2017 Oct 1;40(10):1686-1692. doi: 10.1248/bpb.b17-00215. Epub 2017 Jul 21.

Abstract

Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.

摘要

吗啡广泛用于缓解晚期癌症患者的癌痛。然而,在接受吗啡镇痛的乳腺癌患者中,吗啡是会抑制还是促进癌症进展仍不清楚。因此,我们使用了一种用吗啡和纳洛酮处理的体外模型,来研究吗啡对乳腺癌细胞系MCF-7的影响。MCF-7细胞在第12、24、36、48、60和72小时用不同浓度(0.01至10 μM)的吗啡进行培养。然后,通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法测定细胞活力,并通过流式细胞术(FCM)检测细胞周期和凋亡检测。此外,通过集落形成试验进行细胞增殖检测。在本研究中,我们发现吗啡(0.01至10 μM)可显著降低MCF-7细胞的细胞活力、生长和集落形成率,这与细胞周期停滞在G0/G1和G2/M期以及MCF-7细胞凋亡有一定关系。此外,纳洛酮与吗啡一起不能逆转这些作用,这表明吗啡对MCF-7乳腺癌细胞生长和增殖的抑制可能是其独立作用,与阿片受体无关。吗啡可通过阻断细胞周期抑制细胞生长并促进MCF-7细胞凋亡。因此,吗啡可能无法促进接受吗啡镇痛的乳腺癌患者的癌症进展。

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