甲霉素 A 通过 ATF4-CHOP 轴选择性杀死耐阉割前列腺癌细胞

IF 5.7 2区医学 Q1 Medicine

Cancer Science Pub Date : 2024-09-26 DOI:10.1111/cas.16349

Tomoki Takei, Yuki Hamamura, Hiroshi Hongo, Etsu Tashiro, Masaya Imoto, Takeo Kosaka, Mototsugu Oya

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引用次数: 0

摘要

前列腺癌最初是雄激素依赖性的，但往往会复发为雄激素非依赖性状态，称为阉割抗性前列腺癌（CRPC）。目前已获批准的疗法对 CRPC 的疗效有限，这凸显了对新型治疗策略的需求。为了满足这一需求，我们在之前建立的侵袭性 CRPC 细胞模型中进行了药物筛选。我们发现，福霉素 A 能诱导 CRPC 模型细胞死亡，但不能诱导亲代前列腺癌细胞死亡。此外，福霉素 A 通过诱导内质网应激上调死亡受体 5，激活了 CRPC 模型细胞的 "外源性 "凋亡途径。此外，甲霉素 A 对阉割裸鼠体内的 CRPC 异种移植物具有体内抗肿瘤疗效。因此，我们的研究结果凸显了甲霉素 A 作为 CRPC 治疗药物的潜力。

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Selective killing of castration-resistant prostate cancer cells by formycin A via the ATF4-CHOP axis.

Prostate cancer is initially androgen-dependent but often relapses to an androgen-independent state called castration-resistant prostate cancer (CRPC). Currently approved therapies have limited efficacy against CRPC, highlighting the need for novel therapeutic strategies. To address this need, we conducted a drug screen in our previously established aggressive CRPC cell model. We found that formycin A induced cell death in CRPC model cells but not in parental prostate cancer cells. In addition, formycin A upregulated death receptor 5 through the induction of endoplasmic reticulum stress, activating the "extrinsic" apoptosis pathway in CRPC model cells. Moreover, formycin A showed in vivo antitumor efficacy against CRPC xenografts in castrated nude mice. Thus, our findings highlight the potential of formycin A as a CRPC therapeutic.

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来源期刊

Cancer Science ONCOLOGY-

CiteScore

9.90

自引率

3.50%

发文量

406

审稿时长

17 weeks

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.