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三联苯曲菌素抑制小鼠原位胰腺肿瘤生长并预防转移。

Terphenyllin Suppresses Orthotopic Pancreatic Tumor Growth and Prevents Metastasis in Mice.

作者信息

Zhang Jia, Wang Weiyi, Zhou Yuan, Yang Jing, Xu Jingli, Xu Zhiyuan, Xu Beihua, Yan Li, Cheng Xiang-Dong, Li Minghua, Qin Jiang-Jiang

机构信息

Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan, China.

College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Front Pharmacol. 2020 Apr 8;11:457. doi: 10.3389/fphar.2020.00457. eCollection 2020.

DOI:10.3389/fphar.2020.00457
PMID:32322210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7157903/
Abstract

Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed to develop safe and effective anti-PC therapeutic agents. We have recently identified a novel marine-derived natural product terphenyllin with potent anti-PC activity. The present study was designed to investigate the efficacy and mechanisms of action of terphenyllin in several human PC cell lines and an orthotopic PC mouse model. The results showed that terphenyllin significantly inhibited the viability of all PC cell lines with minimal effects on a normal human pancreatic cell line (HPNE). We next demonstrated the effects of terphenyllin on colony formation, apoptosis, migration, and invasion in both Panc1 and HPAC cell lines in a concentration-dependent manner. Terphenyllin also suppressed the tumor growth and metastasis in the Panc1 orthotopic mouse model. We further showed the profound effects of terphenyllin on the expression of apoptosis-associated proteins, including Bax, Bad, Puma, Bim, Bcl-2, phos-Bcl-2 (Ser70), Bcl-xL, caspase 7, and PARP, which contributed to its anti-PC activity. In summary, terphenyllin suppressed the PC cell growth and metastasis and and may be developed as an anti-PC therapeutic agent in the future.

摘要

胰腺癌（PC）是一种侵袭性致命疾病，转移和复发率很高。然而，大多数PC患者没有有效的治疗选择，尤其是那些患有局部晚期肿瘤和转移性疾病的患者。因此，迫切需要开发安全有效的抗PC治疗药物。我们最近鉴定出一种具有强大抗PC活性的新型海洋来源天然产物terphenyllin。本研究旨在探讨terphenyllin在几种人PC细胞系和原位PC小鼠模型中的疗效及作用机制。结果表明，terphenyllin显著抑制所有PC细胞系的活力，而对正常人胰腺细胞系（HPNE）影响最小。接下来，我们以浓度依赖的方式证明了terphenyllin对Panc1和HPAC细胞系中集落形成、凋亡、迁移和侵袭的影响。Terphenyllin还抑制了Panc1原位小鼠模型中的肿瘤生长和转移。我们进一步展示了terphenyllin对凋亡相关蛋白表达的深远影响，包括Bax、Bad、Puma、Bim、Bcl-2、磷酸化Bcl-2（Ser70）、Bcl-xL、半胱天冬酶7和PARP，这些都促成了其抗PC活性。总之，terphenyllin抑制了PC细胞的生长和转移，未来可能被开发为一种抗PC治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/47c547fa4dcd/fphar-11-00457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/24f9ae4e6072/fphar-11-00457-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/066c8ee3d318/fphar-11-00457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/877bb9b2e24a/fphar-11-00457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/c183b47649ba/fphar-11-00457-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/47c547fa4dcd/fphar-11-00457-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/24f9ae4e6072/fphar-11-00457-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/066c8ee3d318/fphar-11-00457-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/877bb9b2e24a/fphar-11-00457-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/c183b47649ba/fphar-11-00457-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b4/7157903/47c547fa4dcd/fphar-11-00457-g005.jpg

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