Background: Radiotherapy is a key treatment for cancer, effectively controlling local tumor growth through DNA damage that induces senescence or apoptosis in cancer cells. However, radiotherapy can trigger complex cellular reactions, such as cell senescence, which is characterized by irreversible cell cycle arrest and the secretion of pro-inflammatory factors known as the senescent-associated secretory phenotype (SASP).Methods: This study investigates the regulatory role ofALDH1A3, a key enzyme implicated in cancer cell metabolism and radiotherapy resistance, in the induction of senescence and SASP. Using in vitro models, we demonstrate thatALDH1A3knockdown accelerates cellular senescent-like phenotype while regulating the SASP through the cGAS–STING immune response pathway.Results: Our results indicate that whileALDH1A3knockdown promotes senescence, it reduces the secretion of pro-inflammatory factors via inhibition of the cGAS–STING pathway, potentially mitigating SASP-related tumor progression.Conclusions: These findings provide insights into the molecular mechanisms underlying prostate cancer cell senescence and suggest thatALDH1A3could be a potential therapeutic target to enhance the efficacy of radiotherapy while controlling the adverse effects of SASP.
背景：放射治疗是癌症治疗的关键手段，通过诱导癌细胞DNA损伤引发衰老或凋亡，从而有效控制局部肿瘤生长。然而，放疗可能触发复杂的细胞反应，例如细胞衰老。细胞衰老以细胞周期不可逆停滞和促炎因子分泌为特征，这种分泌表型被称为衰老相关分泌表型（SASP）。 方法：本研究探讨了ALDH1A3（一种与癌细胞代谢和放疗抵抗相关的关键酶）在诱导衰老和SASP中的调控作用。通过体外模型，我们发现敲低ALDH1A3可加速细胞衰老样表型，同时通过cGAS–STING免疫应答通路调控SASP。 结果：研究结果表明，虽然ALDH1A3敲低促进衰老进程，但通过抑制cGAS–STING通路减少了促炎因子的分泌，这可能有助于缓解SASP相关的肿瘤进展。 结论：这些发现揭示了前列腺癌细胞衰老的分子机制，并提示ALDH1A3可能成为潜在治疗靶点，在增强放疗疗效的同时控制SASP的不良影响。
ALDH1A3Regulates Cellular Senescence and Senescence-Associated Secretome in Prostate Cancer
肿瘤(癌症)患者之家