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QSOX1 的分子抑制剂抑制肿瘤生长。

Molecular Inhibitor of QSOX1 Suppresses Tumor Growth .

机构信息

School of Life Sciences, Arizona State University, Tempe, Arizona.

RenBio, Inc., New York, New York.

出版信息

Mol Cancer Ther. 2020 Jan;19(1):112-122. doi: 10.1158/1535-7163.MCT-19-0233. Epub 2019 Oct 1.

DOI:10.1158/1535-7163.MCT-19-0233
PMID:31575656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6946859/
Abstract

Quiescin sulfhydryl oxidase 1 (QSOX1) is an enzyme overexpressed by many different tumor types. QSOX1 catalyzes the formation of disulfide bonds in proteins. Because short hairpin knockdowns (KD) of QSOX1 have been shown to suppress tumor growth and invasion and , we hypothesized that chemical compounds inhibiting QSOX1 enzymatic activity would also suppress tumor growth, invasion, and metastasis. High throughput screening using a QSOX1-based enzymatic assay revealed multiple potential QSOX1 inhibitors. One of the inhibitors, known as "SBI-183," suppresses tumor cell growth in a Matrigel-based spheroid assay and inhibits invasion in a modified Boyden chamber, but does not affect viability of nonmalignant cells. Oral administration of SBI-183 inhibits tumor growth in 2 independent human xenograft mouse models of renal cell carcinoma. We conclude that SBI-183 warrants further exploration as a useful tool for understanding QSOX1 biology and as a potential novel anticancer agent in tumors that overexpress QSOX1.

摘要

卷曲螺旋结构域蛋白 18（QSOX1）是一种在许多不同肿瘤类型中过度表达的酶。QSOX1 催化蛋白质中二硫键的形成。由于短发夹 RNA 敲低（KD）QSOX1 已被证明可以抑制肿瘤生长和侵袭，因此，我们假设抑制 QSOX1 酶活性的化学化合物也会抑制肿瘤生长、侵袭和转移。使用基于 QSOX1 的酶测定的高通量筛选揭示了多种潜在的 QSOX1 抑制剂。其中一种抑制剂，称为“SBI-183”，在基于 Matrigel 的球体测定中抑制肿瘤细胞生长，并在改良 Boyden 室中抑制侵袭，但不影响非恶性细胞的活力。SBI-183 的口服给药抑制了 2 种独立的人肾细胞癌异种移植小鼠模型中的肿瘤生长。我们得出结论，SBI-183 值得进一步探索，作为了解 QSOX1 生物学的有用工具，以及作为过度表达 QSOX1 的肿瘤中潜在的新型抗癌剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/e41e9773c433/nihms-1540742-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/3ea42feb1135/nihms-1540742-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/f7c40607681d/nihms-1540742-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/509c4cc99943/nihms-1540742-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/a198a67b5039/nihms-1540742-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/4a46f1e512d9/nihms-1540742-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/e41e9773c433/nihms-1540742-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/3ea42feb1135/nihms-1540742-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/f7c40607681d/nihms-1540742-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/509c4cc99943/nihms-1540742-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/a198a67b5039/nihms-1540742-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/4a46f1e512d9/nihms-1540742-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9401/6946859/e41e9773c433/nihms-1540742-f0006.jpg

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