极源科委会深海极小分子南极磷虾油重大发现

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业内权威《LIPIDS》杂志正式发表出刊来自中国极源科委会团队，历时4年时间完成的“南极磷虾油通过阻断细胞外信号调节蛋白激酶信号通过干扰小鼠结肠癌细胞的增殖和迁移”这一重大医学发现。目前中国南极磷虾产业经历了10余年的发展，中国在南极磷虾捕捞产量已位居世界第二大强国，在国内研发领域定位于南极磷虾生物医药和南极磷虾生命科学的探索处于空白状态，这一极具的创新发现在国内南极磷虾生物科技领域是一次巨大突破，预示着海洋生物功能食品对未来市场的冲击和价值。

doi：10.1002 / lipd.12281。

Krill Oil Perturbs Proliferation and Migration of Mouse Colon CancerCells in vitro by Impeding Extracellular Signal-Regulated Protein K

Weiqiang Jing¹, YuxuanBi¹, GanyuWang¹, ShuyanZeng¹, LihuiHan², HuiYang³, NaWang⁴ YunxueZhao¹²

磷虾油通过阻断细胞外信号调节蛋白激酶信号通过干扰小鼠结肠癌细胞的增殖和迁移

Affiliations

·¹Department of Pharmacology, School of Basic Medical Sciences,Shandong University, Wenhua Xi Road, Jinan, 250012, China.

· ²Department of Immunology, Shandong Provincial Key Laboratory ofInfection and Immunology, School of Basic Medical Sciences, ShandongUniversity, Wenhua Xi Road, Jinan, 250012, China.

·³Department of Radiology, Qilu Hospital, Shandong University,Wenhua Xi Road, Jinan, 250012, China.

·⁴Jinan Jiyuan Biological Technology Co., Ltd, Longao North Road,Jinan, 250102, China.

Abstract

The prevalence of colorectal cancer (CRC) continues to increase.Treatment of CRC remains a significant clinical challenge, and effectivetherapies for advanced CRC are desperately needed. Increasing attention andongoing research efforts have focused on krill oil that may provide healthbenefits to the human body. Here we report that krill oil exerts in vitroanticancer activity through a direct inhibition on proliferation, colonyformation, migration, and invasion of mouse colon cancer cells. Krill oil inhibitedthe proliferation and colony formation of CT-26 colon cancer cells by causingG0/G1 cell cycle arrest and apoptosis. Cell cycle arrest was attributable toreduction of cyclin D1 levels in krill oil-treated cells. Further studiesrevealed that krill oil induced mitochondrial-dependent apoptosis of CT-26cells, including loss of mitochondrial membrane potential, increased cytosoliccalcium levels, activation of caspase-3, and downregulation of anti-apoptoticproteins MCL-1 and BCL-XL. Krill oil suppressed migration of CT-26 cells bydisrupting the microfilaments and microtubules. Extracellular signal-regulatedprotein kinase (ERK) plays crucial roles in regulating proliferation andmigration of cancer cells. We found that krill oil attenuated the activation ofERK signaling pathway to exert the effects on cell cycle, apoptosis, andmigration of colon cancer cells. We speculate that polyunsaturated fatty acidsof krill oil may dampen ERK activation by decreasing the phospholipidsaturation of cell membrane. Although findings from in vitro studies may notnecessarily translate in vivo, our study provides insights into the possibilitythat krill oil or its components could have therapeutic potential in coloncancer.

摘要

结直肠癌(CRC)的患病率持续上升。结直肠癌的治疗仍然是一个重大的临床挑战，晚期结直肠癌急需有效的治疗方法。越来越多的注意力和正在进行的研究集中在可能对人体健康有益的磷虾油上。在这里，我们报道了磷虾油通过直接抑制小鼠结肠癌细胞的增殖、集落形成、迁移和侵袭发挥体外抗癌活性。磷虾油通过抑制CT-26结肠癌细胞的增殖和集落形成，引起G0/G1细胞周期阻滞和凋亡。细胞周期阻滞是由于磷虾油处理细胞中cyclin D1水平的降低。进一步研究发现，磷虾油可诱导CT-26细胞线粒体依赖性凋亡，包括线粒体膜电位的丧失、胞浆钙水平的升高、caspase-3的激活以及抗凋亡蛋白MCL-1和BCL-XL的下调。磷虾油通过破坏微丝和微管来抑制CT-26细胞的迁移。细胞外信号调节蛋白激酶(ERK)在调节癌细胞的增殖和迁移中起着至关重要的作用。我们发现，磷虾油可以减弱ERK信号通路的激活，从而对结肠癌细胞周期、凋亡和迁移产生影响。我们推测，磷虾油中的多不饱和脂肪酸可能通过降低细胞膜磷脂饱和度来抑制ERK的激活。虽然体外研究的结果不一定适用于体内，但我们的研究提供了磷虾油或其成分对结肠癌具有治疗潜力的可能性。

Keywords: Apoptosis; Colorectal cancer; ERK; Krill oil; Migration;Proliferation.