3,4-二氢-6-[4-(3,4-二甲氧基苯甲酰基)-1-哌嗪基]-2(1H)-喹啉酮（维司力农）对在无胸腺裸鼠体内生长的人腺样鳞状癌形成细胞系的抗肿瘤活性特征

Characteristics of antitumor activity of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]- 2(1H)-quinolinone (vesnarinone) against a human adenoid squamous carcinoma-forming cell line grown in athymic nude mice.

作者信息

Sato M, Harada K, Bando T, Shirakami T, Nakashiro K, Yoshida H, Nakai S, Kawai K, Adachi M

机构信息

Second Department of Oral and Maxillofacial Surgery, Tokushima University Schools of Dentistry, Japan.

出版信息

Cancer Lett. 1995 May 4;91(1):1-9. doi: 10.1016/0304-3835(95)03713-7.

DOI:10.1016/0304-3835(95)03713-7

PMID:7750082

Abstract

The tumors produced by transplantation into nude mice of human adenoid squamous carcinoma-forming cell line TYS, presumably derived from a minor salivary gland, were treated with a differentiation-inducing agent, vesnarinone, which was given per o.s. daily at a dose of 200 mg/kg for 35 days. They were then examined morphologically and immunohistochemically. The vesnarinone treatment resulted in a significant suppression of tumor growth. In addition, tumor nests indicating keratinocyte and acinar cell differentiation were often observed in the treated tumors, but not in untreated controls. Tissue sections from vesnarinone-treated and untreated TYS tumors were stained with monoclonal antibody (NAb) directed to carbohydrate antigen LeY or proliferating cell nuclear antigen (PCNA) and with rabbit polyclonal antibody to p53. Antibody staining patterns were compared with morphological characteristics of cells as revealed by hematoxylin and eosin staining, and DNA fragmentation patterns as revealed by 3'-OH nick-end labelling techniques. Tissue sections from vesnarinone-treated TYS tumors showed positive reaction with nick-end labelling and were extensively stained strongly by anti-LeY MAb, whereas the untreated tumors showed negative reaction with nick-end labelling and were infrequently stained by anti-LeY MAb. Within LeY-positive areas of tissue sections from the vesnarinone-treated tumors, keratinocyte and acinar cell differentiation as well as DNA fragmentation were frequently observed, although not all LeY-positive cells showed such signs of apoptosis. LeY-positive cells showed consistent negative staining by anti-PCNA MAb and anti-p53 rabbit serum. From these findings, it can be considered that vesnarinone has differentiation and apoptosis-inducing activity against TYS cells grown in athymic nude mouse.

摘要

将人腺样鳞状癌形成细胞系TYS（可能来源于小唾液腺）移植到裸鼠体内所产生的肿瘤，用分化诱导剂维司那林进行治疗，维司那林经口每日给药，剂量为200mg/kg，持续35天。然后对其进行形态学和免疫组织化学检查。维司那林治疗导致肿瘤生长显著受到抑制。此外，在经治疗的肿瘤中经常观察到显示角质形成细胞和腺泡细胞分化的肿瘤巢，而在未治疗的对照中则未观察到。用针对碳水化合物抗原LeY或增殖细胞核抗原（PCNA）的单克隆抗体（NAb）以及针对p53的兔多克隆抗体对维司那林治疗和未治疗的TYS肿瘤的组织切片进行染色。将抗体染色模式与苏木精和伊红染色所显示的细胞形态特征以及3'-OH缺口末端标记技术所显示的DNA片段化模式进行比较。维司那林治疗的TYS肿瘤的组织切片显示缺口末端标记呈阳性反应，并且被抗LeY单克隆抗体广泛强烈染色，而未治疗的肿瘤缺口末端标记呈阴性反应，并且很少被抗LeY单克隆抗体染色。在维司那林治疗的肿瘤的组织切片的LeY阳性区域内，经常观察到角质形成细胞和腺泡细胞分化以及DNA片段化，尽管并非所有LeY阳性细胞都显示出这种凋亡迹象。LeY阳性细胞对抗PCNA单克隆抗体和抗p53兔血清呈一致的阴性染色。从这些发现可以认为，维司那林对无胸腺裸鼠体内生长的TYS细胞具有分化和诱导凋亡活性。