Rhee Yun-Hee, Moon Jeong-Hwan, Choi Sun-Hyang, Ahn Jin-Chul
1 Beckman Laser Institute Korea, Dankook University , Cheonan, Chungnam, Republic of Korea.
2 Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Dankook University , Cheonan, Republic of Korea.
Photomed Laser Surg. 2016 Jun;34(6):229-35. doi: 10.1089/pho.2015.3968. Epub 2016 Apr 14.
We assessed the cause of increased tumor after low-level laser therapy (LLLT) by histological analysis.
LLLT is a nonthermal phototherapy used in several medical applications, including wound healing, reduction of pain, and amelioration of oral mucositis. We discovered by accident that LLLT increased tumor size while testing a photodynamic therapy (PDT) model for the treatment of thyroid cancer. Although therapeutic effects of LLLT on cancer or dysplastic cells have been studied, LLLT has been recently reported to stimulate the aggressiveness of the tumor.
The anaplastic thyroid cancer cell line FRO was injected into thyroid glands of nude mice orthotopically and then laser irradiation was performed with 0, 15, and 30 J/cm(2) (100 mW/cm(2)) on the thyroid after 10 days. The tumor volume was measured for 4 weeks and the thyroid tissues underwent histological analysis. We observed that proliferation of FRO cells and macrophage infiltration was increased with energy delivery to the thyroid glands. We also assessed overproliferated FRO cells using an immunohistochemical staining with hypoxia inducible factor 1α (HIF-1α), p-Akt, vascular endothelial growth factor (VEGF), and transforming growth factor β1 (TGF-β1).
HIF-1α and p-Akt were elevated after LLLT, which suggested that the phosphorylation of Akt by LLLT led to the activation of HIF-1α. Moreover, TGF-β1 expression was decreased after LLLT, which led to loss of cell cycle regulation.
In conclusion, LLLT led to a decrease in TGF-β1 and increase of p-Akt/HIF-1α which resulted to overproliferation and angiogenesis of anaplastic thyroid carcinoma (ATC). Therefore, we suggest that LLLT can influence cancer aggressiveness associated with TGF-β1 and Akt/HIF-1α cascades in some poorly differentiated head and neck cancers.
我们通过组织学分析评估了低强度激光治疗（LLLT）后肿瘤增大的原因。
LLLT是一种非热光疗法，用于多种医学应用，包括伤口愈合、减轻疼痛和改善口腔黏膜炎。我们在测试用于治疗甲状腺癌的光动力疗法（PDT）模型时意外发现LLLT会增大肿瘤大小。尽管已经研究了LLLT对癌细胞或发育异常细胞的治疗效果，但最近有报道称LLLT会刺激肿瘤的侵袭性。
将间变性甲状腺癌细胞系FRO原位注射到裸鼠的甲状腺中，10天后对甲状腺进行0、15和30 J/cm²（100 mW/cm²）的激光照射。测量肿瘤体积4周，并对甲状腺组织进行组织学分析。我们观察到随着向甲状腺输送能量，FRO细胞的增殖和巨噬细胞浸润增加。我们还使用缺氧诱导因子1α（HIF-1α）、磷酸化Akt、血管内皮生长因子（VEGF）和转化生长因子β1（TGF-β1）的免疫组织化学染色评估过度增殖的FRO细胞。
LLLT后HIF-1α和磷酸化Akt升高，这表明LLLT使Akt磷酸化导致HIF-1α激活。此外，LLLT后TGF-β1表达降低，导致细胞周期调控丧失。
总之，LLLT导致TGF-β1减少和磷酸化Akt/HIF-1α增加，从而导致间变性甲状腺癌（ATC）过度增殖和血管生成。因此，我们认为LLLT可能会影响某些低分化头颈癌中与TGF-β1和Akt/HIF-1α级联相关的癌症侵袭性。
