Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Spain.
Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08003 Barcelona, Spain.
Int J Mol Sci. 2023 Jan 30;24(3):2580. doi: 10.3390/ijms24032580.
In cancer, overactivation of poly (ADPribose) polymerases (PARP) plays a relevant role in DNA repair. We hypothesized that treatment with the PARP inhibitor rucaparib may reduce tumor burden via several biological mechanisms (apoptosis and oxidative stress) in mice. In lung tumors (LP07 lung adenocarcinoma) of mice treated/non-treated (control animals) with PARP inhibitor (rucaparib,150 mg/kg body weight/24 h for 20 day), PARP activity and expression, DNA damage, apoptotic nuclei, cell proliferation, and redox balance were measured using immunoblotting and immunohistochemistry. In lung tumors of rucaparib-treated mice compared to non-treated animals, tumor burden, PARP activity, and cell proliferation decreased, while DNA damage, TUNEL-positive nuclei, protein oxidation, and superoxide dismutase content (SOD)2 increased. In this experiment on lung adenocarcinoma, the pharmacological PARP inhibitor rucaparib elicited a significant improvement in tumor size, probably through a reduction in cell proliferation as a result of a rise in DNA damage and apoptosis. Oxidative stress and SOD2 also increased in response to treatment with rucaparib within the tumor cells of the treated mice. These results put the line forward to the contribution of PARP inhibitors to reduced tumor burden in lung adenocarcinoma. The potential implications of these findings should be tested in clinical settings of patients with lung tumors.
在癌症中，聚（ADP-核糖）聚合酶（PARP）的过度激活在 DNA 修复中起着重要作用。我们假设，PARP 抑制剂鲁卡帕尼的治疗可能通过几种生物学机制（细胞凋亡和氧化应激）在小鼠中减少肿瘤负担。在接受/未接受 PARP 抑制剂（鲁卡帕尼，150mg/kg 体重/24 小时，共 20 天）治疗的小鼠的肺肿瘤（LP07 肺腺癌）中，使用免疫印迹和免疫组织化学测量 PARP 活性和表达、DNA 损伤、凋亡核、细胞增殖和氧化还原平衡。与未治疗的动物相比，鲁卡帕尼治疗的小鼠的肺肿瘤中的肿瘤负担、PARP 活性和细胞增殖减少，而 DNA 损伤、TUNEL 阳性核、蛋白氧化和超氧化物歧化酶 2 含量（SOD2）增加。在这项肺腺癌的实验中，药理学 PARP 抑制剂鲁卡帕尼显著改善了肿瘤大小，这可能是由于 DNA 损伤和细胞凋亡增加导致细胞增殖减少所致。在接受治疗的小鼠的肿瘤细胞中，氧化应激和 SOD2 也因鲁卡帕尼的治疗而增加。这些结果表明，PARP 抑制剂在减少肺腺癌中的肿瘤负担方面具有重要作用。这些发现的潜在意义应在肺肿瘤患者的临床环境中进行测试。
