香椿叶提取物对7,12-二甲基苯并[a]蒽诱导的仓鼠颊囊鳞状细胞癌的化学预防作用。

Chemopreventive effect of Toona sinensis leaf extract on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch squamous cell carcinogenesis.

作者信息

Wang Wen-Chen, Chen Ching-Yi, Hsu Hseng-Kuang, Lin Li-Min, Chen Yuk-Kwan

机构信息

Division of Oral Pathology and Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Oral and Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dentistry, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.

Division of Oral Pathology and Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Oral and Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

Arch Oral Biol. 2016 Oct;70:130-142. doi: 10.1016/j.archoralbio.2016.06.015. Epub 2016 Jun 15.

DOI:10.1016/j.archoralbio.2016.06.015

PMID:27348052

Abstract

OBJECTIVE

Toona sinensis leaf extract (TSL) has been shown to have anti-tumor effects on cancer cell lines. This study aimed to investigate the chemopreventive potential and the underlying mechanism of TSL during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis.

METHODS

One hundred hamsters were divided into control (n=30), carcinogenic (n=20), preventive (n=42), and therapeutic (n=8) groups. The animals in carcinogenic and preventive groups were administered reverse osmosis water (carcinogenic group) or TSL (1g/kg bw) (preventive group) by gavage daily for 4 weeks, and their bilateral pouches were painted with a 0.5% DMBA solution for 4, 9, and 12 weeks. The animals in the therapeutic group were treated with DMBA for 12 weeks prior to TSL administration for 4 weeks. Expression levels of survivin, X chromosome-linked inhibitor of apoptosis (XIAP), proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins were analyzed by immunohistochemistry. Apoptotic activity was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, cytochrome C, and poly (ADP-ribose) polymerase (PARP).

RESULTS

In the preventive group, the results showed significant decreases not only in the incidences of squamous cell carcinoma (SCC) (50%) and epithelial dysplasia (62.5%) but also in the tumor number, tumor volume, tumor burden, and the severity of dysplastic lesions. The down-regulation of survivin, XIAP, PCNA, iNOS, and COX-2 proteins and the increased apoptotic activity indicated anti-proliferative and apoptosis-inducing abilities of TSL on DMBA-induced HBP carcinogenesis.

CONCLUSIONS

The results suggested that TSL might be a promising candidate for the prevention of oral cancer.

摘要

目的

香椿叶提取物（TSL）已被证明对癌细胞系具有抗肿瘤作用。本研究旨在探讨TSL在7,12-二甲基苯并[a]蒽（DMBA）诱导的仓鼠颊囊（HBP）癌变过程中的化学预防潜力及其潜在机制。

方法

将100只仓鼠分为对照组（n = 30）、致癌组（n = 20）、预防组（n = 42）和治疗组（n = 8）。致癌组和预防组的动物每天经口灌胃给予反渗透水（致癌组）或TSL（1g/kg体重）（预防组），持续4周，然后在第4、9和12周时，其双侧颊囊涂抹0.5% DMBA溶液。治疗组的动物在给予TSL治疗4周前，先接受DMBA处理12周。通过免疫组织化学分析存活素、X染色体连锁凋亡抑制蛋白（XIAP）、增殖细胞核抗原（PCNA）、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）蛋白表达水平。采用末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）法、细胞色素C和聚（ADP-核糖）聚合酶（PARP）检测凋亡活性。

结果

在预防组中，结果显示不仅鳞状细胞癌（SCC）发病率（50%）和上皮发育异常（62.5%）显著降低，而且肿瘤数量、肿瘤体积、肿瘤负荷以及发育异常病变的严重程度也显著降低。存活素、XIAP、PCNA、iNOS和COX-2蛋白的下调以及凋亡活性增加表明TSL对DMBA诱导的HBP癌变具有抗增殖和诱导凋亡的能力。