Positive therapy of andrographolide in vocal fold leukoplakia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Otolaryngological Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Jue
J
Xu
Laboratory of Molecular Medicine, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Tao
T
Xue
Department of Hepatobiliary Surgery and Molecular Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Ying
Y
Bao
Department of Pharmacy, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Dong-Hai
DH
Wang
Department of Otolaryngological Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Bing-Liang
BL
Ma
Department of Otolaryngological Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Chen-Yi
CY
Yin
Department of Pharmacy, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Guang-Hui
GH
Yang
Department of Otolaryngological Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Gang
G
Ren
Department of Otolaryngological Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Long-Jiang
LJ
Lan
Department of Otolaryngological Surgery, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Jian-Qiu
JQ
Wang
Department of Pathology, First People's Hospital Affiliated to Huzhou University, Huzhou, China.
Xiao-Lan
XL
Zhang
School of Food Science and Pharmacy, Zhejiang Ocean University, Zhoushan, China. Electronic address: oceanow@163.com.
Yu-Qin
YQ
Zhao
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001706:Biopsy; D004224:Diterpenes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007822:Laryngeal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007828:Laryngoscopy; D007971:Leukoplakia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013237:Stereoisomerism; D013997:Time Factors; D016896:Treatment Outcome; D014827:Vocal Cords; D014833:Voice Quality
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; C030419:andrographolide