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表达干扰素-β基因的人脐带基质干细胞通过凋亡抑制乳腺癌细胞。

Human umbilical cord matrix-derived stem cells expressing interferon-β gene inhibit breast cancer cells via apoptosis.

作者信息

Shen Ching-Ju, Chan Te-Fu, Chen Chien-Chung, Hsu Yi-Chiang, Long Cheng-Yu, Lai Chung-Sheng

机构信息

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

Oncotarget. 2016 Jun 7;7(23):34172-9. doi: 10.18632/oncotarget.8997.

Abstract

Human umbilical cord mesenchymal stem cells (hUCMSCs) derived from the umbilical cord matrix have been reported to be used as anti-tumor gene carrier for attenuation of tumor growth, which extends the half-life and lowers the unexpected cytotoxicity of the gene in vivo. Interferon-β (IFNβ) is known to possess robust anti-tumor effects on different types of cancer cell lines in vitro. The present study was aimed to investigate the anti-tumor effect of IFNβ gene-transfected hUCMSCs (IFNβ-hUCMSCs) on breast cancer cells with emphasis on triple negative breast carcinoma. Our findings revealed that the co-culture of IFNβ-hUCMSCs with the human triple negative breast carcinoma cell lines MDA-MB-231 or Hs578T significantly inhibited growth of both carcinoma cells. In addition, the culture medium conditioned by these cells also significantly suppressed the growth and induced apoptosis of both carcinoma cells. Further investigation showed that the suppressed growth and the apoptosis induced by co-culture of IFNβ-hUCMSCs or conditioned medium were abolished by pretreating anti-IFNβ neutralizing antibody. These findings indicate that IFNβ-hUCMSCs triggered cell death of breast carcinoma cells through IFN-β production, thereby induced apoptosis and suppressed tumor cell growth. In conclusion, we demonstrated that IFNβ-hUCMSCs inhibited the growth of breast cancer cells through apoptosis. With potent anti-cancer activity, it represents as an anti-cancer cytotherapeutic modality against breast cancer.

摘要

据报道,源自脐带基质的人脐带间充质干细胞(hUCMSCs)可作为抗肿瘤基因载体,用于减缓肿瘤生长,这延长了基因在体内的半衰期并降低了意外的细胞毒性。已知干扰素-β(IFNβ)在体外对不同类型的癌细胞系具有强大的抗肿瘤作用。本研究旨在探讨IFNβ基因转染的hUCMSCs(IFNβ-hUCMSCs)对乳腺癌细胞的抗肿瘤作用,重点是三阴性乳腺癌。我们的研究结果显示,IFNβ-hUCMSCs与人三阴性乳腺癌细胞系MDA-MB-231或Hs578T共培养可显著抑制两种癌细胞的生长。此外,这些细胞条件培养基也显著抑制了两种癌细胞的生长并诱导其凋亡。进一步研究表明,用抗IFNβ中和抗体预处理可消除IFNβ-hUCMSCs或条件培养基共培养所诱导的生长抑制和凋亡。这些发现表明,IFNβ-hUCMSCs通过产生IFN-β触发乳腺癌细胞死亡,从而诱导凋亡并抑制肿瘤细胞生长。总之,我们证明了IFNβ-hUCMSCs通过凋亡抑制乳腺癌细胞的生长。因其具有强大的抗癌活性,它代表了一种针对乳腺癌的抗癌细胞治疗方式。

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