Paraoxonase 2 (PON2) is a multifunctional intracellular enzyme that has received growing attention for its ability to modulate various aspects of normal and malignant cellular physiology. Recent research has revealed that PON2 is upregulated in tissues from patients with various types of solid tumors and hematologic cancers, likely due to its ability to suppress oxidative stress and evade apoptosis. However, the effects of PON2 on pulmonary oncogenesis are unknown. Here, we conducted studies to investigate how PON2 influences lung cancer cell proliferation in vitro and lung tumorigenesis in vivo using a variety of cellular and animal models. It was found that PON2 expression deficiency hampered the proliferation of cultured lung cancer cells with concomitant cell cycle arrest at the G1 phase. In addition, the loss of endogenous PON2 expression impaired key aspects of oxidative metabolism in lung adenocarcinoma cells. Moreover, we investigated how the interplay between PON2 expression in lung tumors and host mice influences lung tumor initiation and progression. PON2 status in both transplanted tumor cells and mice failed to influence the development of subcutaneously grafted Lewis lung carcinoma (LLC) tumors, orthotopically implanted LLC tumors, and oncogenic Kras-driven primary lung adenocarcinoma tumors. Importantly, the frequencies of tumor-infiltrating myeloid subsets that include myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages were not impacted by PON2 expression in LLC tumor-bearing mice. Overall, our studies indicate that PON2 plays a limited role in murine lung tumorigenesis.

对氧磷酶 2 (PON2) 是一种多功能细胞内酶，因其调节正常和恶性细胞生理学各个方面的能力而受到越来越多的关注。最近的研究表明，PON2 在各种类型实体瘤和血液癌症患者的组织中表达上调，这可能是由于其抑制氧化应激和逃避细胞凋亡的能力。然而，PON2 对肺肿瘤发生的影响尚不清楚。在这里，我们使用多种细胞和动物模型进行了研究，以调查 PON2 如何影响体外肺癌细胞增殖和体内肺肿瘤发生。研究发现，PON2 表达缺陷会阻碍培养的肺癌细胞的增殖，并伴随细胞周期停滞在 G1 期。此外，内源性 PON2 表达的丧失会损害肺腺癌细胞氧化代谢的关键方面。此外，我们研究了肺肿瘤和宿主小鼠中 PON2 表达之间的相互作用如何影响肺肿瘤的发生和进展。移植肿瘤细胞和小鼠中的 PON2 状态未能影响皮下移植的 Lewis 肺癌 (LLC) 肿瘤、原位植入的 LLC 肿瘤和致癌的 Kras 驱动的原发性肺腺癌肿瘤的发展。重要的是，在 LLC 荷瘤小鼠中，包括骨髓源性抑制细胞 (MDSC) 和肿瘤相关巨噬细胞在内的肿瘤浸润骨髓亚群的频率不受 PON2 表达的影响。总的来说，我们的研究表明 PON2 在小鼠肺部肿瘤发生中发挥有限的作用。