王红阳院士团队发现维生素C优先杀死“吃货”肿瘤干细胞!
中国生物技术网 · 2018/01/15
2018年1月8日,海军军医大学东方肝胆外科医院王红阳院士研究团队在《自然》子刊《npj-肿瘤精准医疗》上发表重磅文章,该研究发现维生素C优先杀死肝癌的肿瘤干细胞并改善患者预后。


图片来源:期刊(doi:10.1038/s41698-017-0044-8)

本文转载自“中国生物技术网”,作者:王红阳院士研究团队。

肿瘤干细胞在启动肿瘤形成和生长中起着决定性作用,现有的治疗措施尚无法针对肿瘤干细胞发挥作用,这可能是导致肝癌复发和耐药的主要原因。2017年Cancer cell、Cell、Nature接连喜讯,维生素C再次登上抗癌“神坛”。该文章中,研究人员通过体内和体外实验,惊喜地发现与肿瘤干细胞普遍耐受的传统化疗药顺铂(Cisplatin)相反,高浓度的维生素C(VC)对肝癌干细胞的杀伤效果明显优于非干细胞,说明肝癌干细胞对维生素C的毒性更加敏感(下图左)。进一步探究机制发现维生素C进入细胞内的关键通道——维生素C转运体2(SVCT-2)不仅在肝癌干细胞中高表达,还促进其自我更新,也就是说肝癌干细胞有一张更大的“嘴巴”来吃维生素C(下图中)。


研究者证实SVCT-2表达越高,维生素C进入细胞也越多,细胞死得也越快(下图右)。进入细胞的维生素C通过增加细胞内活性氧(ROS),引起DNA损伤和能量耗竭,最终导致细胞周期阻滞和凋亡。因此,肿瘤干细胞好比一个大嘴巴的维生素C“吃货”,因为更贪吃,所以死得更快!

为了进一步证明维生素C通过SVCT-2优先杀死肝癌的肿瘤干细胞,研究者构建了个体化肿瘤动物模型,即来源于患者肿瘤组织的异种移植(PDX)模型,并发现维生素C对肝癌的疗效与其SVCT-2的表达水平成正相关,即维生素C对SVCT-2表达高的肿瘤抑制效果更好,并能显著降低肿瘤干细胞比例。

最后研究者通过对613例行肝癌切除术患者的回顾性研究表明,术后接受静脉滴注2g维生素C治疗患者的无病生存期(DFS)明显延长(下图左)。2g维生素C在人体内所能达到的血药浓度被证实在体外对肝癌细胞有显著杀伤作用。尽管仍需进一步的临床试验证实,静脉注射高浓度的维生素C有可能成为一种廉价、高效、低副作用的治疗方法,为肝癌患者带来福音。


王红阳院士研究团队长期致力于肝癌的精准治疗研究,维生素C优先消除肝癌中肿瘤干细胞的研究成果将为解决肝癌转移和复发提供新的治疗策略。东方肝胆外科医院杨文副研究员为该文的共同通讯作者,研究生吕洪伟、王长征和方田为该文的共同第一作者。

所有文章仅代表作者观点,不代表本站立场。如若转载请联系原作者。
  • 2018/03/09
    中枢神经系统中,髓鞘对神经元功能至关重要。在一些脱髓鞘疾病如多发性硬化(MS)中,免疫系统攻击自身神经系统导致神经髓鞘的破坏和白质损伤,是仅次于创伤的中青年人致残原因,有着“死不了的癌症”之称。
  • 2017/08/23
    8月21日,Nature期刊上又一篇文章揭示维生素C抗白血病机制,来自美国德州大学儿童西南医学中心(CRI)的研究人员发现,干细胞能吸收异常高水平的抗坏血酸盐(维生素C),然后调节自身功能,从而抑制白血病的发展。
  • 2017/08/21
    “静脉注射高剂量的维生素C,有望阻止白血病干细胞增殖。”这是《Cell》期刊最新一篇在线文章的研究成果。科学家们发现,维生素C能够“告诉”骨髓中有缺陷的干细胞发育成熟并正常死亡,而不是无限增殖导致血液癌症。
查看更多
  • Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2

    Vitamin C (L-ascorbic acid, ascorbate, VC) is a potential chemotherapeutic agent for cancer patients. However, the anti-tumor effects of pharmacologic VC on hepatocellular carcinoma (HCC) and liver cancer stem cells (CSCs) remain to be fully elucidated. Panels of human HCC cell lines as well as HCC patient-derived xenograft (PDX) models were employed to investigate the anti-tumor effects of pharmacologic VC. The use of VC and the risk of HCC recurrence were examined retrospectively in 613 HCC patients who received curative liver resection as their initial treatment. In vitro and in vivo experiments further demonstrated that clinically achievable concentrations of VC induced cell death in liver cancer cells and the response to VC was correlated with sodium-dependent vitamin C transporter 2 (SVCT-2) expressions. Mechanistically, VC uptake via SVCT-2 increased intracellular ROS, and subsequently caused DNA damage and ATP depletion, leading to cell cycle arrest and apoptosis. Most importantly, SVCT-2 was highly expressed in liver CSCs, which promoted their self-renewal and rendered them more sensitive to VC. In HCC cell lines xenograft models, as well as in PDX models, VC dramatically impaired tumor growth and eradicated liver CSCs. Finally, retrospective cohort study showed that intravenous VC use was linked to improved disease-free survival (DFS) in HCC patients (adjusted HR = 0.622, 95% CI 0.487 to 0.795, p < 0.001). Our data highlight that pharmacologic VC can effectively kill liver cancer cells and preferentially eradicate liver CSCs, which provide further evidence supporting VC as a novel therapeutic strategy for HCC treatment.

    展开 收起
发表评论 我在frontend\modules\comment\widgets\views\文件夹下面 test