極源科委會(huì)深海極小分子南極磷蝦油重大發(fā)現(xiàn)

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業(yè)內(nèi)權(quán)威《LIPIDS》雜志正式發(fā)表出刊來(lái)自中國(guó)極源科委會(huì)團(tuán)隊(duì)，歷時(shí)4年時(shí)間完成的“南極磷蝦油通過(guò)阻斷細(xì)胞外信號(hào)調(diào)節(jié)蛋白激酶信號(hào)通過(guò)干擾小鼠結(jié)腸癌細(xì)胞的增殖和遷移”這一重大醫(yī)學(xué)發(fā)現(xiàn)。目前中國(guó)南極磷蝦產(chǎn)業(yè)經(jīng)歷了10余年的發(fā)展，中國(guó)在南極磷蝦捕撈產(chǎn)量已位居世界第二大強(qiáng)國(guó)，在國(guó)內(nèi)研發(fā)領(lǐng)域定位于南極磷蝦生物醫(yī)藥和南極磷蝦生命科學(xué)的探索處于空白狀態(tài)，這一極具的創(chuàng)新發(fā)現(xiàn)在國(guó)內(nèi)南極磷蝦生物科技領(lǐng)域是一次巨大突破，預(yù)示著海洋生物功能食品對(duì)未來(lái)市場(chǎng)的沖擊和價(jià)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

磷蝦油通過(guò)阻斷細(xì)胞外信號(hào)調(diào)節(jié)蛋白激酶信號(hào)通過(guò)干擾小鼠結(jié)腸癌細(xì)胞的增殖和遷移

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

結(jié)直腸癌(CRC)的患病率持續(xù)上升。結(jié)直腸癌的治療仍然是一個(gè)重大的臨床挑戰(zhàn)，晚期結(jié)直腸癌急需有效的治療方法。越來(lái)越多的注意力和正在進(jìn)行的研究集中在可能對(duì)人體健康有益的磷蝦油上。在這里，我們報(bào)道了磷蝦油通過(guò)直接抑制小鼠結(jié)腸癌細(xì)胞的增殖、集落形成、遷移和侵襲發(fā)揮體外抗癌活性。磷蝦油通過(guò)抑制CT-26結(jié)腸癌細(xì)胞的增殖和集落形成，引起G0/G1細(xì)胞周期阻滯和凋亡。細(xì)胞周期阻滯是由于磷蝦油處理細(xì)胞中cyclin D1水平的降低。進(jìn)一步研究發(fā)現(xiàn)，磷蝦油可誘導(dǎo)CT-26細(xì)胞線粒體依賴性凋亡，包括線粒體膜電位的喪失、胞漿鈣水平的升高、caspase-3的激活以及抗凋亡蛋白MCL-1和BCL-XL的下調(diào)。磷蝦油通過(guò)破壞微絲和微管來(lái)抑制CT-26細(xì)胞的遷移。細(xì)胞外信號(hào)調(diào)節(jié)蛋白激酶(ERK)在調(diào)節(jié)癌細(xì)胞的增殖和遷移中起著至關(guān)重要的作用。我們發(fā)現(xiàn)，磷蝦油可以減弱ERK信號(hào)通路的激活，從而對(duì)結(jié)腸癌細(xì)胞周期、凋亡和遷移產(chǎn)生影響。我們推測(cè)，磷蝦油中的多不飽和脂肪酸可能通過(guò)降低細(xì)胞膜磷脂飽和度來(lái)抑制ERK的激活。雖然體外研究的結(jié)果不一定適用于體內(nèi)，但我們的研究提供了磷蝦油或其成分對(duì)結(jié)腸癌具有治療潛力的可能性。

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

? 2020 AOCS.