抗癌新策略?修复生物钟,延缓肿瘤恶化!
2017/02/20
一旦外压或者基因突变导致细胞周期紊乱,细胞便容易失去控制而发生癌变。科学家们已经知道生物钟紊乱与肿瘤恶化速度密切相关。那么,如果修复癌细胞的生物钟,能否逆转癌变、延缓肿瘤发展呢?近期,来自于麦克吉尔大学的研究团队以患癌小鼠为模型,证实重塑癌细胞的生物钟,能够使其恢复正常。


讲究养生的人都大多都格外重视遵循生物钟。人只有顺应体内的生物钟,才能保证健康的身体、高效的工作、愉悦的心情。同时生物钟也控制着细胞的生长周期,一旦外压或者基因突变导致细胞周期紊乱,细胞便容易失去控制而发生癌变。

过去的研究也多展现出“昼夜节律紊乱与肿瘤恶化速度密切相关”的迹象。但是,如果我们修复细胞的生物钟,能否逆转癌变、延缓肿瘤发展呢?

近期,来自于麦克吉尔大学的研究团队以患癌小鼠为模型,证实重塑癌细胞的生物钟,能够使其恢复正常。

团队负责人、精神病学系教授Nicolas Cermakian博士表示:“科学家们曾推测,一旦生物钟发生故障,肿瘤生长会加速。但是却从未有研究证实这一假说。现在,借助化学或者热处理,我们能够成功修复癌细胞的生命时钟,使其恢复至正常。在这种情况下,肿瘤的生长速度几乎下降了一半。”

研究团队以“Enhancing Circadian Clock Function in Cancer Cells Inhibits Tumor Growth”为题,将相关研究成果于2月14日发表在《BMC Biology》期刊。

他们发现,肿瘤细胞中的生物钟基因被抑制。当他们以诱导昼夜节律的药物/方法处理癌细胞后,例如地塞米松、腺苷酸环化酶激活剂和热休克,研究结果表明,这些方法能够修复生物钟,刺激细胞周期相关基因的表达,从而促使更多的细胞进入G1期。研究人员表示,这种方法能够减缓肿瘤的增殖。

Cermakian实验室的博士后Silke Kiessling成功在体内恢复了两种肿瘤细胞的生物钟。他们以小鼠为模型,发现通过药物治疗一周后,患癌小鼠体内的肿瘤比对照组的小了约1/3。

值得注意的是,当沉默肿瘤细胞的Bmal1基因,地塞米松抑制肿瘤细胞生长的效果会消失。这意味着,地塞米松的抗癌原理并不是通过启动细胞凋亡或者诱导免疫细胞实现的,它能够重启细胞周期,实现抑制肿瘤生长的目标。从本质上讲,地塞米松靶向的是肿瘤内在的生物钟!

研究人员表示,修复生物钟或将成为治疗癌症的新方法,它能够减缓肿瘤生长或转移,为手术、放化疗等传统疗法“申请”到更多的时间。当然,这种预想需要更多的动物和临床试验加以证实。

参考资料:

Cancer Runs Slower When Its Clock Is Ticking

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  • Enhancing circadian clock function in cancer cells inhibits tumor growth

    Background Circadian clocks control cell cycle factors, and circadian disruption promotes cancer. To address whether enhancing circadian rhythmicity in tumor cells affects cell cycle progression and reduces proliferation, we compared growth and cell cycle events of B16 melanoma cells and tumors with either a functional or dysfunctional clock. Results We found that clock genes were suppressed in B16 cells and tumors, but treatments inducing circadian rhythmicity, such as dexamethasone, forskolin and heat shock, triggered rhythmic clock and cell cycle gene expression, which resulted in fewer cells in S phase and more in G1 phase. Accordingly, B16 proliferation in vitro and tumor growth in vivo was slowed down. Similar effects were observed in human colon carcinoma HCT-116 cells. Notably, the effects of dexamethasone were not due to an increase in apoptosis nor to an enhancement of immune cell recruitment to the tumor. Knocking down the essential clock gene Bmal1 in B16 tumors prevented the effects of dexamethasone on tumor growth and cell cycle events. Conclusions Here we demonstrated that the effects of dexamethasone on cell cycle and tumor growth are mediated by the tumor-intrinsic circadian clock. Thus, our work reveals that enhancing circadian clock function might represent a novel strategy to control cancer progression.

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