曾升平部分对 DMBA 诱导的仓鼠颊囊癌变的抑制作用。

Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters.

机构信息

Department of Periodontology & Oral Medicine, Capital Medical University School of Stomatology, Beijing 100050, China.

出版信息

Chin Med J (Engl). 2012 Jan;125(2):332-7.

Abstract

BACKGROUND

Zengshengping (ZSP) tablets had inhibitory effects on oral precancerous lesions by reducing the incidence of oral cancer. However, the severe liver toxicity caused by systemic administration of ZSP limits the long-term use of this anti-cancer drug. The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of extracts from ZSP, a Chinese herbal drug, on 7, 12-dimethlbenz(a)anthracene (DMBA) induced oral tumors in hamsters. The study also investigated the anti-cancer mechanisms of the ZSP extracts on oral carcinogenesis.

METHODS

DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6 - 8 weeks old) three times per week for six weeks in order to induce the development of oral tumors. Different fractions of ZSP were either applied topically to the oral tumor lesions or fed orally at varying dosages to animals with oral tumors for 18 weeks. Tumor volume was measured by histopathological examination. Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels. The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting.

RESULTS

Topical application of DMBA to the left pouch of hamsters induced oral tumor formation. Animals treated with DMBA showed a loss in body weight while animals treated with ZSP maintained normal body weights. Both the ZSP n-butanol fraction and water fraction significantly reduced tumor volume by 32.6% (P < 0.01) and 22.9% (P < 0.01) respectively. Topical application of ZSP also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of MAPK. In addition, ZSP promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production.

CONCLUSION

The n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.

摘要

背景

曾升平（ZSP）片通过降低口腔癌的发病率对口腔癌前病变有抑制作用。然而，ZSP 的全身给药引起的严重肝毒性限制了这种抗癌药物的长期使用。本研究旨在评估 ZSP 提取物局部应用于二甲基苯并蒽（DMBA）诱导的仓鼠口腔肿瘤的肿瘤抑制作用。该研究还探讨了 ZSP 提取物对口腔癌变的抗癌机制。

方法

每周三次将 0.5%的 DMBA 涂于叙利亚金仓鼠（6-8 周龄）颊囊以诱导口腔肿瘤的发生。不同的 ZSP 馏分分别局部应用于口腔肿瘤病变或口服给予有口腔肿瘤的动物，为期 18 周。通过组织病理学检查测量肿瘤体积。通过计数 BrdU 标记细胞和通过 Western 印迹法测定丝裂原活化蛋白激酶（MAPK）蛋白水平来评估肿瘤细胞增殖。还通过 Western 印迹法测量凋亡标志物 Caspase-3 和调节蛋白 Bcl-2 蛋白的蛋白水平。

结果

将 DMBA 涂于左侧颊囊可诱导口腔肿瘤形成。用 DMBA 处理的动物体重减轻，而用 ZSP 处理的动物保持正常体重。ZSP 的正丁醇馏分和水馏分分别显著降低肿瘤体积 32.6%（P<0.01）和 22.9%（P<0.01）。ZSP 的局部应用也显著减少了口腔肿瘤病变中的 BrdU 阳性细胞数量，并降低了 MAPK 的表达水平。此外，ZSP 通过增加 Caspase-3 表达和减少 Bcl-2 蛋白产生来促进肿瘤细胞凋亡。