Aslan Volkan, Usta Duygu Deniz, Yar Sağlam Atiye Seda, Özet Ahmet, Sütcüoglu Osman, Dikmen Kürşat, Özdemir Nuriye
Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Türkiye.
Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06560 Ankara, Türkiye.
Int J Mol Sci. 2025 Sep 18;26(18):9086. doi: 10.3390/ijms26189086.
Supportive agents, such as vitamin B12 (cobalamin, B12) and granulocyte colony-stimulating factor (G-CSF), are widely used during chemotherapy; however, their direct effects on tumor biology are not well understood. We evaluated the impact of pharmacological B12 and G-CSF, alone or in combination with cisplatin, on hormone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells, conducting in vitro assays of cell viability, cytotoxicity, caspase activation, mitochondrial membrane potential, and cytolytic protein expression. Neither B12 nor G-CSF alone induced cytotoxicity; instead, both promoted proliferation in a dose- and time-dependent manner. When combined with cisplatin, they consistently attenuated drug-induced cytotoxicity, suppressed caspase-3/-8/-9 activation, preserved mitochondrial integrity, and reduced perforin/granzyme expression, exhibiting stronger effects in MCF-7 cells. G-CSF markedly increased proliferation (>130% at 50 ng/mL), while B12 modestly enhanced viability and mitigated cisplatin-induced damage, particularly in triple-negative cells. These findings indicate that B12 and G-CSF can impair cisplatin efficacy by blunting apoptotic signaling and mitochondrial injury in different breast cancer subtypes. These preclinical findings warrant prospective, biomarker-driven in vivo and clinical studies to delineate the clinical contexts in which B12 and G-CSF can be safely integrated into supportive care without compromising antitumor efficacy.
支持性药物,如维生素B12(钴胺素,B12)和粒细胞集落刺激因子(G-CSF),在化疗期间被广泛使用;然而,它们对肿瘤生物学的直接影响尚未得到充分了解。我们评估了药理学上的B12和G-CSF单独或与顺铂联合使用对激素受体阳性(MCF-7)和三阴性(MDA-MB-231)乳腺癌细胞的影响,进行了细胞活力、细胞毒性、半胱天冬酶激活、线粒体膜电位和溶细胞蛋白表达的体外试验。单独使用B12或G-CSF均未诱导细胞毒性;相反,两者均以剂量和时间依赖性方式促进增殖。当与顺铂联合使用时,它们一致减弱了药物诱导的细胞毒性,抑制了半胱天冬酶-3/-8/-9的激活,保持了线粒体完整性,并降低了穿孔素/颗粒酶的表达,在MCF-7细胞中表现出更强的作用。G-CSF显著增加增殖(50 ng/mL时>130%),而B12适度提高活力并减轻顺铂诱导的损伤,特别是在三阴性细胞中。这些发现表明,B12和G-CSF可通过减弱不同乳腺癌亚型中的凋亡信号和线粒体损伤来损害顺铂疗效。这些临床前发现需要进行前瞻性的、由生物标志物驱动的体内和临床研究,以确定在哪些临床情况下B12和G-CSF可以安全地纳入支持性治疗而不影响抗肿瘤疗效。