School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Division of Oral Pathology & Maxillofacial Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Oral Dis. 2019 Apr;25(3):758-771. doi: 10.1111/odi.13036. Epub 2019 Feb 6.
Oral cancer is a common cancer with a high mortality rate. While surgery is the most effective treatment for oral cancer, it frequently causes deformity and dysfunction in the orofacial region. In this study, methyl aminolevulinate photodynamic therapy (MAL-PDT) as a prevention tool against progression of precancerous lesion to oral cancer was explored.
For in vitro studies, we evaluated the effects of MAL-PDT on viability of DOK oral precancerous cells by XTT, cell morphology by TEM, and intracellular signaling pathways by flow cytometry, Western blotting, and immunofluorescence. For in vivo study, DMBA was used to induce oral precancerous lesions in hamsters followed by MAL-PDT treatment. We measured tumor size and body weight weekly. After sacrifice, buccal pouch lesions were processed for H&E stain and immunohistochemistry analysis.
MAL-PDT induced autophagic cell death in DOK oral precancerous cells. The autophagy-related markers LC3II and p62/SQSTM1 and autophagosome formation in DOK cells were increased after MAL-PDT treatment. In vivo, Metvix -PDT treatment decreased tumor growth and enhanced LC3II expression in hamster buccal pouch tumors induced by DMBA.
Our in vitro and in vivo results suggest that MAL-PDT may provide an effective therapy for oral precancerous lesions through induction of autophagic cell death.
口腔癌是一种死亡率较高的常见癌症。虽然手术是治疗口腔癌最有效的方法，但它经常导致口腔区域的畸形和功能障碍。在本研究中，探索了甲氨基乙酰丙酸光动力疗法（MAL-PDT）作为预防癌前病变进展为口腔癌的工具。
在体外研究中，我们通过 XTT 评估了 MAL-PDT 对 DOK 口腔癌前细胞活力的影响，通过 TEM 评估了细胞形态，通过流式细胞术、Western blot 和免疫荧光评估了细胞内信号通路。在体内研究中，使用 DMBA 诱导仓鼠口腔癌前病变，然后进行 MAL-PDT 治疗。我们每周测量肿瘤大小和体重。处死动物后，处理颊囊病变进行 H&E 染色和免疫组化分析。
MAL-PDT 诱导 DOK 口腔癌前细胞发生自噬性细胞死亡。MAL-PDT 处理后，DOK 细胞中的自噬相关标志物 LC3II 和 p62/SQSTM1 以及自噬体形成增加。在体内，Metvix-PDT 治疗可减少 DMBA 诱导的仓鼠颊囊肿瘤的生长，并增强 LC3II 的表达。
我们的体外和体内结果表明，MAL-PDT 可能通过诱导自噬性细胞死亡为口腔癌前病变提供一种有效的治疗方法。
