衰老基于抗癌疗法的成功依赖于它们的抗增殖能力和诱导抗肿瘤免疫反应的能力。事实上，基因毒性药物诱导的细胞衰老增加了NK细胞激活配体在多发性骨髓瘤（MM）细胞上的表达，增强了NK细胞的识别和效应功能。细胞衰老经历形态学变化和依赖于环境的功能多样化，获得了分泌被称为衰老相关分泌表型（SASP）的大量分子的能力，影响周围细胞。最近，外泌体被认为是SASP因子，有助于调节各种细胞功能。特别是，证据表明外泌体microRNA在影响癌症多个方面起着关键作用。在此，我们证明了多柔比星（doxorubicin）处理MM细胞会导致miR-433在外泌体中富集，进而引发旁观衰老。我们的分析揭示了邻近MM细胞上衰老表型的建立与p53和p21无关，并与CDK-6下调有关。值得注意的是，miR-433依赖性衰老不会诱导MM细胞上激活配体的上调。总的来说，我们的发现强调了miR-433富集的外泌体增强多柔比星介导的细胞衰老的可能性。

The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. Senescent cells undergo morphological change and context-dependent functional diversification, acquiring the ability to secrete a vast pool of molecules termed the senescence-associated secretory phenotype (SASP), which affects neighboring cells. Recently, exosomes have been recognized as SASP factors, contributing to modulating a variety of cell functions. In particular, evidence suggests a key role for exosomal microRNAs in influencing many hallmarks of cancer. Herein, we demonstrate that doxorubicin treatment of MM cells leads to the enrichment of miR-433 into exosomes, which in turn induces bystander senescence. Our analysis reveals that the establishment of the senescent phenotype on neighboring MM cells is p53- and p21-independent and is related to CDK-6 down-regulation. Notably, miR-433-dependent senescence does not induce the up-regulation of activating ligands on MM cells. Altogether, our findings highlight the possibility of miR-433-enriched exosomes to reinforce doxorubicin-mediated cellular senescence.