Skaličková Markéta, Abramenko Nikita, Charnavets Tatsiana, Vellieux Frédéric, Leischner Fialová Jindřiška, Kučnirová Kateřina, Kejík Zdeněk, Masařík Michal, Martásek Pavel, Pacak Karel, Pacák Tomáš, Jakubek Milan
BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic.
Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, 120 00 Prague, Czech Republic.
ACS Omega. 2025 Apr 15;10(16):15935-15946. doi: 10.1021/acsomega.4c05483. eCollection 2025 Apr 29.
Despite the natural ability of the immune system to recognize cancer and, in some patients, even to eliminate it, cancer cells have acquired numerous evading mechanisms. With the increasing knowledge and focus shifting from targeting rapidly proliferating cells with chemotherapy to modulating the immune system, there have been recent efforts to integrate (e.g., simultaneously or sequentially) various therapeutic approaches. Combining the oncolytic activity of some chemotherapeutics with immunostimulatory molecules, so-called chemoimmunotherapy, is an attractive strategy. An example of such an immunostimulatory molecule is polyinosinic:polycytidylic acid [Poly(I:C)], a synthetic analogue of double-stranded RNA characterized by rapid nuclease degradation hampering its biological activity. This study investigated the possible interactions of tetracycline and anthracycline chemotherapeutics with different commercial Poly(I:C) molecules and protection against nuclease degradation. Fluorescence spectroscopy and circular dichroism revealed an interaction of all of the selected chemotherapeutics with Poly(I:C)s and the ability of doxycycline and minocycline to prolong the resistance to RNase cleavage, respectively. The partial protection was observed as well.
尽管免疫系统具有识别癌症的天然能力,甚至在某些患者中能够消除癌症,但癌细胞已经获得了多种逃避机制。随着知识的不断增加以及关注点从用化疗靶向快速增殖细胞转向调节免疫系统,最近人们一直在努力整合(例如同时或相继)各种治疗方法。将某些化疗药物的溶瘤活性与免疫刺激分子相结合,即所谓的化学免疫疗法,是一种有吸引力的策略。这种免疫刺激分子的一个例子是聚肌苷酸:聚胞苷酸[聚(I:C)],它是双链RNA的合成类似物,其特点是核酸酶快速降解会阻碍其生物活性。本研究调查了四环素和蒽环类化疗药物与不同商业聚(I:C)分子之间可能的相互作用以及对核酸酶降解的保护作用。荧光光谱法和圆二色性显示,所有选定的化疗药物与聚(I:C)之间存在相互作用,并且强力霉素和米诺环素分别具有延长对核糖核酸酶切割抗性的能力。也观察到了部分保护作用。