Development of photodynamic therapy to early stage oral cancer using drug delivery system

使用药物输送系统开发早期口腔癌光动力疗法

• 批准号: 11470438
• 负责人: TORATANI Shigeaki
• 金额: $ 3.78万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470438/
• 关键词: photodynamic therapy; liposome; hematoporphyrin derivative; active oxigen; lipid composition of membrane; squamous cell carcinoma; adenocarcinoma from salivary gland; 光照射; 扁平上皮癌

Photodynamic therapy (PDT) using both hematoporphyrin derivative (HPD) and photoradiation has had a high rate of effectiveness in combatting early stage cancers. We have studied, to apply this therapy to treatment of oral cancer, on verious type of cultured carcinoma cells derived from oral cancers.It has been revealed that squamous cell carcinoma cells (SCC) exhibited high sensitivity to PDT in comparison with salivary gland-derived adenocarcinoma cells (SAC). It became clear that SAC exhibited an increased level of reduced glutathion and glutathion peroxidase activity in comparison to those of SCC.The SCC which showed decreased sensitivity to PDT, exhibited a extremerly high level of glutathion S-transferase activity. Consequenly, the function of glutathion cascade were factors determining photosensitivity of the cells. In addition, the SCC demonstrated an increased intracellular level of drug compare to that SAC.So we have investigated lipid composition of cell-membrane of both cells under serum-free culture. It became evident that 60% of membrane lipids of SCC was phospholipids (PL) and 80% of those of SAC was neutral lipids (NL). The NL/PL ratio indicated that SCC showed low levels but SAC showed remarkably high levels. These result indicated that the cytotoxity of PDT correlated with the intracellular levels of drug resulted from the difference of membrane hydrophobicity.Thus, we have designed liposome which is comparable to the lipid composition of SCC cell membrane, constructed the liposome-entrapped anti-cancer drugs and examined sensitivity to this liposome of both SCC and SAC by growth assay. As the result, the liposome-entrapped drug exhibited enhanced cytotoxicity on SCC compare to either drug alone or drug-liposome mixture.

使用血卟啉衍生物（HPD）和光辐射的光动力疗法（PDT）在对抗早期癌症方面具有高效率。为了将这种疗法应用于口腔癌的治疗，我们对来自口腔癌的各种类型的培养癌细胞进行了研究，发现鳞状细胞癌细胞（SCC）对PDT的敏感性高于唾液腺来源的腺癌细胞（SAC）。很明显，SAC表现出减少谷胱甘肽和谷胱甘肽过氧化物酶活性的增加水平相比，SCC。SCC表现出对PDT的敏感性下降，表现出极高水平的谷胱甘肽S-转移酶活性。因此，谷胱甘肽级联反应的功能是决定细胞光敏性的因素。另外，SCC细胞内药物浓度较SAC高，因此我们在无血清培养条件下研究了SCC和SAC细胞膜的脂质组成。结果表明，SCC的膜脂中60%为磷脂（PL），SAC的膜脂中80%为中性脂（NL）。NL/PL比值表明SCC显示低水平，但SAC显示显著高水平。因此，我们设计了与SCC细胞膜脂质组成相似的脂质体，构建了脂质体包埋抗癌药物的脂质体，并通过生长实验检测了SCC和SAC对脂质体的敏感性。结果表明，脂质体包封的药物对SCC的细胞毒性比单独药物或药物-脂质体混合物增强。

项目成果

Shigeaki TORATANI: "Effect of photodynamic action with pheophorbide-a on human oral carcinoma cells in serum-free culture."Tiss.Cult.Res.Commun.. 18・4. 345-352 (1999)

Shigeaki TORATANI：“脱镁叶绿酸-a 的光动力作用对无血清培养物中人口腔癌细胞的影响”。Tiss.Cult.Res.Commun. 18・4 (1999)。

Toratani, S., Kimoto, N., Shinki, T.and Okamoto, T.: "Effect of photodynamic action with pheophorbide-a on human oral carcinoma cells in serum-free culture."Tiss.Cult.Res.Commun.. 18. 345-352 (1999)

Toratani, S.、Kimoto, N.、Shinki, T. 和 Okamoto, T.：“脱镁叶绿酸-a 的光动力作用对无血清培养物中人口腔癌细胞的影响。”Tiss.Cult.Res.Commun.

Shigeaki TORATANI: "Effect of photodynamic action with pheophorbide-a on human oral carcinoma cells in serum-free culture."Tiss.Cult.Res.Commun.. 18. 345-352 (1999)

Shigeaki TORATANI：“脱镁叶绿酸-a 的光动力作用对无血清培养物中人口腔癌细胞的影响。”Tiss.Cult.Res.Commun.. 18. 345-352 (1999)

S. Toratani et al.: "Effect of photodynamic therapy action with pheophorbide-a on human oral carcinoma cells in serum-free culture"Tiss. Cult. Res. Commun.. 18・4. 345-352 (1999)

S. Toratani 等：“脱镁叶绿酸-a 对无血清培养物中的人口腔癌细胞的影响”Tiss Commun. 18・4 (1999)。