Vergel Mar, Marin Juan J, Estevez Purificacion, Carnero Amancio
Instituto de Biomedicina de Sevilla, Hospital Universitario virgen del Rocio, 41013 Sevilla, Spain.
J Aging Res. 2010 Dec 30;2011:725365. doi: 10.4061/2011/725365.
Somatic cells show a spontaneous decline in growth rate in continuous culture. This is not related to elapsed time but to an increasing number of population doublings, eventually terminating in a quiescent but viable state termed replicative senescence. These cells are commonly multinucleated and do not respond to mitogens or apoptotic stimuli. Cells displaying characteristics of senescent cells can also be observed in response to other stimuli, such as oncogenic stress, DNA damage, or cytotoxic drugs and have been reported to be found in vivo. Most tumors show unlimited replicative potential, leading to the hypothesis that cellular senescence is a natural antitumor program. Recent findings suggest that cellular senescence is a natural mechanism to prevent undesired oncogenic stress in somatic cells that has been lost in malignant tumors. Given that the ultimate goal of cancer research is to find the definitive cure for as many tumor types as possible, exploration of cellular senescence to drive towards antitumor therapies may decisively influence the outcome of new drugs. In the present paper, we will review the potential of cellular senescence to be used as target for anticancer therapy.
体细胞在连续培养中显示出生长速率的自发下降。这与经过的时间无关，而是与群体倍增次数的增加有关，最终终止于一种静止但仍存活的状态，称为复制性衰老。这些细胞通常是多核的，并且对有丝分裂原或凋亡刺激无反应。在对其他刺激（如致癌应激、DNA损伤或细胞毒性药物）的反应中也可观察到表现出衰老细胞特征的细胞，并且据报道在体内也能发现。大多数肿瘤显示出无限的复制潜力，这导致了细胞衰老可能是一种天然抗肿瘤程序的假说。最近的研究结果表明，细胞衰老是一种防止体细胞中出现不良致癌应激的天然机制，而这种机制在恶性肿瘤中已经丧失。鉴于癌症研究的最终目标是尽可能找到针对多种肿瘤类型的确切治愈方法，探索利用细胞衰老来推动抗肿瘤治疗可能会对新药的疗效产生决定性影响。在本文中，我们将综述细胞衰老作为抗癌治疗靶点的潜力。
