Xu Jue, Xue Tao, Bao Ying, Wang Dong-Hai, Ma Bing-Liang, Yin Chen-Yi, Yang Guang-Hui, Ren Gang, Lan Long-Jiang, Wang Jian-Qiu, Zhang Xiao-Lan, Zhao Yu-Qin
Department of Otolaryngological Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Laboratory of Molecular Medicine, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Am J Otolaryngol. 2014 Mar-Apr;35(2):77-84. doi: 10.1016/j.amjoto.2013.12.006. Epub 2013 Dec 20.
Vocal fold leukoplakia is a premalignant precursor of squamous cell carcinoma. Although many efforts have been contributed to therapy of this disease, none exhibits a satisfactory result. The aims of this study were to investigate the effectiveness and feasibility of andrographolide therapy in vocal fold leukoplakia and to explore the preliminary mechanism underlying.
Forty-one eligible patients were enrolled in the study. The patients were treated for 10-minute exposures of 5 ml (25mg/ml) andrographolide injection aerosols twice a day, and 2 weeks was considered as one treatment course. Electronic laryngoscope was used to observe the condition of vocal fold leukoplakia during the treatment. Every patient received one or two treatment courses, and the follow-up was carried out for 12 months. Toxic reactions of treatments were evaluated on the basis of the standards of the United States MD Anderson Cancer Center. Moreover, laryngeal carcinoma cell line Hep2 was applied to explore the mechanism of effect of andrographolide. Anti-proliferative effect on Hep2, cell nuclear morphology, express of mitogen-activated protein kinases (MAPK) and pro-apoptotic protein were detected after andrographolide treatment.
We found that andrographolide exhibited significant curative effects on treatments, which were accompanied by thinning of the lesion of leukoplakia, reduction in the whitish surface area, and return of pink or red epithelium. A complete response up to 85% was observed, and no toxic side effect events occurred during the study. No patient with a complete response had a recurrence in the follow-up. Moreover, cellular experiments in Hep2 indicated that andrographolide activated MAPK pathway and caspase cascade, and finally induced apoptosis in laryngeal carcinoma cell.
The advantages of andrographolide are connected with minimally invasive and localized character of the treatment and no damage of collagenous tissue structures, which are more convenient and less painful for patients. These results suggest that andrographolide treatment is a viable strategy for curing vocal fold leukoplakia.
声带白斑是鳞状细胞癌的癌前病变。尽管在该疾病的治疗方面已经做出了许多努力,但均未取得令人满意的结果。本研究的目的是探讨穿心莲内酯治疗声带白斑的有效性和可行性,并探索其潜在的初步机制。
41例符合条件的患者纳入本研究。患者接受5ml(25mg/ml)穿心莲内酯注射液雾化吸入治疗,每次10分钟,每天2次,2周为一个疗程。治疗期间使用电子喉镜观察声带白斑情况。每位患者接受1或2个疗程的治疗,并进行12个月的随访。根据美国MD安德森癌症中心的标准评估治疗的毒性反应。此外,应用喉癌细胞系Hep2探索穿心莲内酯的作用机制。检测穿心莲内酯处理后对Hep2的抗增殖作用、细胞核形态、丝裂原活化蛋白激酶(MAPK)表达及促凋亡蛋白表达。
我们发现穿心莲内酯治疗具有显著疗效,表现为白斑病变变薄、白色表面积减少以及粉红色或红色上皮恢复。观察到完全缓解率高达85%,且研究期间未发生毒副作用事件。完全缓解的患者在随访中均未复发。此外,Hep2细胞实验表明,穿心莲内酯激活MAPK通路和半胱天冬酶级联反应,最终诱导喉癌细胞凋亡。
穿心莲内酯的优势在于治疗具有微创和局部化特点,且不损伤胶原组织结构,对患者而言更方便、痛苦更小。这些结果表明,穿心莲内酯治疗是治愈声带白斑的一种可行策略。