Department of Respiration, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, People's Republic of China.
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, People's Republic of China.
J Cancer Res Clin Oncol. 2021 Feb;147(2):493-498. doi: 10.1007/s00432-020-03467-5. Epub 2020 Nov 21.
Lung cancer is a leading cause of cancer-associated deaths worldwide. Lung cancer may lead to circadian disruption, which could contribute to the development of lung cancer. Recently, several studies using animal models indicated that tumors influence systemic circadian homeostasis in remote tissues. However, it is unclear whether carcinoma of the lungs influences remote circadian rhythm, whether this effect exists in humans, and whether signals from the tumor travel through the blood. In this study, we used a cell-based assay to determine whether serum from patients with lung adenocarcinoma could modulate the molecular clock. We found that the daily oscillation period of Bmal1 was significantly lengthened following treatment with serum from untreated lung adenocarcinoma patients. In addition, heat inactivation of this serum abolished the effect, suggesting that a heat-sensitive circulating factor(s) is present in the serum of untreated lung adenocarcinoma patients. Using real-time PCR, we also examined the mRNA abundance of Bmal1, Cry1, and Per1 in human osteosarcoma u2os cell line, HUVECs and A549 cell lines. The expression of Bmal1 was changed in A549 cells in the presence of sera from lung adenocarcinoma patients. Our study revealed a direct effect of serum from lung adenocarcinoma patients on the molecular clock.
肺癌是全球癌症相关死亡的主要原因。肺癌可能导致昼夜节律紊乱，从而导致肺癌的发生。最近，一些使用动物模型的研究表明，肿瘤会影响远处组织的系统昼夜平衡。然而，目前尚不清楚肺癌是否会影响远处的昼夜节律，这种影响是否存在于人类中，以及肿瘤信号是否通过血液传播。在这项研究中，我们使用基于细胞的测定法来确定来自肺腺癌患者的血清是否可以调节分子钟。我们发现，未经处理的肺腺癌患者的血清处理后，Bmal1 的每日振荡周期明显延长。此外，该血清的热失活消除了这种作用，表明未经处理的肺腺癌患者的血清中存在热敏感的循环因子（s）。使用实时 PCR，我们还检查了人骨肉瘤 u2os 细胞系、HUVECs 和 A549 细胞系中 Bmal1、Cry1 和 Per1 的 mRNA 丰度。存在来自肺腺癌患者的血清时，A549 细胞中的 Bmal1 表达发生了变化。我们的研究揭示了肺腺癌患者血清对分子钟的直接影响。
