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Alloferon通过调节SLC6A14的表达影响胰腺癌的化学敏感性。

Alloferon Affects the Chemosensitivity of Pancreatic Cancer by Regulating the Expression of SLC6A14.

作者信息

Jo Hyejung, Lee Dahae, Go Cheolhyeon, Jang Yoojin, Bae Suhyun, Agura Tomoyo, Hong Jiye, Kang Dongmin, Kim Yejin, Kang Jae Seung

机构信息

Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Korea.

Department of Psychological and Brain Sciences, College of Arts and Sciences, Boston University, Boston, MA 02215, USA.

出版信息

Biomedicines. 2022 May 11;10(5):1113. doi: 10.3390/biomedicines10051113.

Abstract

Pancreatic cancer (PCa), one of the most malignant solid tumors, has a high mortality rate. Although there have been many trials of chemotherapeutic drugs such as gemcitabine, the mortality rates remain significantly higher than for other types of cancer. Therefore, more effective ways of improving conventional therapy for PCa are needed. Cancer cells take up large amounts of glutamine to drive their rapid proliferation. Recent studies show that the amino acid transporter SLC6A14 is upregulated in some cancers alongside glutamine metabolism. Alloferon, a peptide isolated from the insect immune system, exerts anti-viral and anti-inflammatory effects via its immunomodulatory function. In addition, it has anti-tumoral effects, although the underlying mechanisms are largely unknown. Therefore, we investigated the effects of alloferon on the PCa cell lines Panc-1 and AsPC-1. Exposure of these cells to alloferon for 3 weeks led to the downregulation of SLC6A14 expression and decreased glutamine uptake. Given that SLC6A14 plays a role in tumor progression and survival by promoting glutamine uptake into cancer cells, alloferon could be a potential adjuvant for the chemotherapeutic drug gemcitabine.

摘要

胰腺癌(PCa)是最具恶性的实体瘤之一,死亡率很高。尽管已经对吉西他滨等化疗药物进行了许多试验,但死亡率仍显著高于其他类型的癌症。因此,需要更有效的方法来改进胰腺癌的传统治疗。癌细胞摄取大量谷氨酰胺以驱动其快速增殖。最近的研究表明,氨基酸转运体SLC6A14在一些癌症中与谷氨酰胺代谢一起上调。Alloferon是一种从昆虫免疫系统中分离出的肽,通过其免疫调节功能发挥抗病毒和抗炎作用。此外,它具有抗肿瘤作用,尽管其潜在机制 largely unknown。因此,我们研究了Alloferon对胰腺癌细胞系Panc-1和AsPC-1的影响。将这些细胞暴露于Alloferon 3周导致SLC6A14表达下调和谷氨酰胺摄取减少。鉴于SLC6A14通过促进癌细胞摄取谷氨酰胺在肿瘤进展和存活中发挥作用,Alloferon可能是化疗药物吉西他滨的潜在佐剂。 (注:“largely unknown”直译为“很大程度上未知”,此处保留英文未翻译,因为从语境看可能是原文有误,若按正常翻译会影响整体逻辑通顺度)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cd6/9138528/38aff8dae043/biomedicines-10-01113-g001.jpg

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