Autophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death‐associated protein 1) is a proline‐rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.

中文翻译：

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DAP1负调节豆蔻素在SKOV3细胞中诱导的自噬。

自噬与包括卵巢癌在内的多种人类肿瘤的形成和发展密切相关。作为该过程的主要调节剂，mTOR（雷帕霉素的哺乳动物靶标）的作用已得到充分证明。小豆蔻素是植物中的一种类黄酮，它对自噬的诱导和癌细胞的抗增殖都有作用。但是，具体机制仍不清楚。DAP1（死亡相关蛋白1）是富含脯氨酸的蛋白，参与细胞生长的调节和程序性细胞死亡，包括自噬和凋亡。这项研究的目的是调查DAP1是否参与了豆蔻素在肿瘤细胞中诱导的增殖抑制和自噬。使用在线生物信息学工具，我们发现DAP1表达与卵巢癌患者的生存密切相关。我们的研究表明，豆蔻素诱导的自噬与mTOR抑制有关，而DAP1参与了这一过程。DAP1沉默可降低细胞增殖，但可增强小豆蔻素在SKOV3细胞中的抗增殖作用。在SKOV3细胞中，DAP1沉默可提高自噬水平。值得注意的是，小豆蔻素在DAP1小干扰RNA组中显示出较高的自噬通量。两者合计，我们的结果表明DAP1负调控豆蔻素诱导的自噬，它可能是卵巢癌治疗的潜在目标。在SKOV3细胞中，DAP1沉默可提高自噬水平。值得注意的是，小豆蔻素在DAP1小干扰RNA组中显示出较高的自噬通量。两者合计，我们的结果表明DAP1负调控豆蔻素诱导的自噬，它可能是卵巢癌治疗的潜在目标。在SKOV3细胞中，DAP1沉默可提高自噬水平。值得注意的是，小豆蔻素在DAP1小干扰RNA组中显示出较高的自噬通量。两者合计，我们的结果表明DAP1负调控豆蔻素诱导的自噬，它可能是卵巢癌治疗的潜在目标。