The prevalence of colorectal cancer (CRC) continues to increase. Treatment of CRC remains a significant clinical challenge, and effective therapies for advanced CRC are desperately needed. Increasing attention and ongoing research efforts have focused on krill oil that may provide health benefits to the human body. Here we report that krill oil exerts in vitro anticancer activity through a direct inhibition on proliferation, colony formation, migration, and invasion of mouse colon cancer cells. Krill oil inhibited the proliferation and colony formation of CT‐26 colon cancer cells by causing G0/G1 cell cycle arrest and apoptosis. Cell cycle arrest was attributable to reduction of cyclin D1 levels in krill oil‐treated cells. Further studies revealed that krill oil induced mitochondrial‐dependent apoptosis of CT‐26 cells, including loss of mitochondrial membrane potential, increased cytosolic calcium levels, activation of caspase‐3, and downregulation of anti‐apoptotic proteins MCL‐1 and BCL‐XL. Krill oil suppressed migration of CT‐26 cells by disrupting the microfilaments and microtubules. Extracellular signal‐regulated protein kinase (ERK) plays crucial roles in regulating proliferation and migration of cancer cells. We found that krill oil attenuated the activation of ERK signaling pathway to exert the effects on cell cycle, apoptosis, and migration of colon cancer cells. We speculate that polyunsaturated fatty acids of krill oil may dampen ERK activation by decreasing the phospholipid saturation of cell membrane. Although findings from in vitro studies may not necessarily translate in vivo, our study provides insights into the possibility that krill oil or its components could have therapeutic potential in colon cancer.

中文翻译：

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磷虾油通过阻碍细胞外信号调节蛋白激酶信号通路干扰体外小鼠结肠癌细胞的增殖和迁移

结直肠癌 (CRC) 的患病率继续增加。CRC 的治疗仍然是一项重大的临床挑战，迫切需要针对晚期 CRC 的有效疗法。越来越多的关注和正在进行的研究工作集中在磷虾油上，它可以为人体带来健康益处。在这里我们报告磷虾油在体外发挥作用通过直接抑制小鼠结肠癌细胞的增殖、集落形成、迁移和侵袭来发挥抗癌活性。磷虾油通过引起 G0/G1 细胞周期停滞和凋亡来抑制 CT-26 结肠癌细胞的增殖和集落形成。细胞周期停滞可归因于磷虾油处理细胞中细胞周期蛋白 D1 水平的降低。进一步的研究表明，磷虾油诱导 CT-26 细胞的线粒体依赖性细胞凋亡，包括线粒体膜电位的丧失、细胞溶质钙水平的增加、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。我们发现磷虾油减弱了 ERK 信号通路的激活，从而对结肠癌细胞的细胞周期、凋亡和迁移产生影响。我们推测磷虾油的多不饱和脂肪酸可能通过降低细胞膜的磷脂饱和度来抑制 ERK 的活化。虽然调查结果来自体外研究不一定能转化为体内，我们的研究提供了对磷虾油或其成分在结肠癌中具有治疗潜力的可能性的见解。