Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Anticancer Res. 2024 Jul;44(7):2827-2836. doi: 10.21873/anticanres.17095.
BACKGROUND/AIM: A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells.
Pancreatic cancer cell lines were treated with or without DUV. TLK1 expression and phosphorylation in the two groups were examined. Then, these cancer cell lines were treated with thioridazine (THD), DUV or both. Thereafter, cytomorphology and apoptosis were assessed. Several proteins related to DNA damage, were analyzed in cancer cells treated with DUV and THD. Tumors in a subcutaneous xenograft model were treated with THD, DUV, or both for six weeks.
DUV irradiation induced the phosphorylation of TLK1 in pancreatic cancer cell lines. Cytomorphology was significantly changed in pancreatic cancer cells treated with DUV and THD. TLK1 inhibition enhanced DUV irradiation-induced apoptosis in cancer cells. Interestingly, CHK1 and pCHK1 expression was suppressed after TLK1 inhibition. In addition, inhibition of MRE11 led to a decrease in the expression of CHK1 and pCHK1, accompanied by a notable increase in apoptosis. In the subcutaneous xenograft models, the tumor volume in the DUV and THD groups was lower than that in the other groups.
TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.
背景/目的：深紫外（DUV）发光二极管（LED）是一种能够辐射波长在 250nm 至 350nm 之间的电磁波的设备。Tousled-like 激酶 1（TLK1）编码一种核丝氨酸/苏氨酸激酶，被认为会影响癌症中 DUV 照射的效果。本研究旨在阐明 TLK1 与癌症细胞中 DUV 照射诱导的 DNA 损伤的相互作用。
用或不用 DUV 处理胰腺癌细胞系。检查两组中 TLK1 的表达和磷酸化。然后，用噻氯匹定（THD）、DUV 或两者联合处理这些癌细胞系。然后评估细胞形态和细胞凋亡。分析用 DUV 和 THD 处理的癌细胞中与 DNA 损伤相关的几种蛋白质。用 THD、DUV 或两者联合处理皮下异种移植模型中的肿瘤 6 周。
DUV 照射诱导胰腺癌细胞系中 TLK1 的磷酸化。用 DUV 和 THD 处理的胰腺癌细胞的细胞形态发生了显著变化。TLK1 抑制增强了癌细胞中 DUV 照射诱导的细胞凋亡。有趣的是，TLK1 抑制后 CHK1 和 pCHK1 的表达受到抑制。此外，MRE11 的抑制导致 CHK1 和 pCHK1 的表达减少，同时细胞凋亡显著增加。在皮下异种移植模型中，DUV 和 THD 组的肿瘤体积低于其他组。
TLK1 磷酸化是 DUV 照射的一个重要事件。DUV 照射联合 TLK1 抑制在胰腺癌细胞中具有治疗潜力。
