Schwartz J L, Flynn E, Trickler D, Shklar G
Harvard School of Dental Medicine, Boston, MA 02115.
Nutr Cancer. 1991;16(2):107-24. doi: 10.1080/01635589109514149.
The purpose of this study was to extend the knowledge of the antitumor activity of liposomes and to identify, for the first time, the antitumor effect of liposomes with the antioxidant beta-carotene. The administration of the carotenoid encapsulated in in liposomes has the advantages of quantitation, facilitation, and most importantly an increased therapeutic response, resulting in the accentuation of regression of carcinoma in the hamster pouch. Tumors induced after the application of the carcinogen 7,12-dimethylbenz[alpha]anthracene (0.5%) were injected with liposomes composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine in a ratio of 1:1:1 (large unilamellar vesicles). Tumor-bearing animals were divided into four groups, each containing 10 hamsters. The group treated with the liposomes of beta-carotene exhibited a significantly lower tumor burden (approx 5,000-fold difference) than the control tumor group. Electron- and light-micrographic analyses were used to substantiate the gross observations of tumor regression. It was noted that the carcinoma cells endocytozed liposomes in increased numbers compared with normal mucosa treated with liposomes. In addition, non-tumor-bearing hamsters injected with beta-carotene liposomes or liposomes alone did not exhibit any pathological change to the normal mucosa. An inflammatory infiltrate consisting of mononuclear cells, mast cells, and some polymorphonuclear leukocytes was noted, and degranulating polymorphonuclear leukocytes and mast cells and eosinophils predominated in the tumor controls (7,12-dimethylbenz[alpha]anthracene treated only). Notably, not all areas of degenerating dysplasia or early carcinoma exhibited a dense inflammatory response adjacent to the mucosa after the injection of beta-carotene liposomes. The results demonstrate a selective nontoxic therapy to regress experimental oral cancer.
本研究的目的是拓展对脂质体抗肿瘤活性的认识，并首次确定含有抗氧化剂β-胡萝卜素的脂质体的抗肿瘤作用。脂质体包裹的类胡萝卜素给药具有定量、便利等优点，最重要的是能增强治疗反应，从而使仓鼠颊囊癌的消退更为显著。将致癌剂7,12-二甲基苯并[a]蒽（0.5%）诱发的肿瘤注射由磷脂酰胆碱、磷脂酰丝氨酸和磷脂酰乙醇胺按1:1:1比例组成的脂质体（大单层囊泡）。荷瘤动物分为四组，每组10只仓鼠。用β-胡萝卜素脂质体治疗的组与对照肿瘤组相比，肿瘤负荷显著降低（相差约5000倍）。通过电子显微镜和光学显微镜分析来证实肿瘤消退的大体观察结果。值得注意的是，与用脂质体处理的正常黏膜相比，癌细胞摄取脂质体的数量增加。此外，注射β-胡萝卜素脂质体或单独脂质体的无瘤仓鼠对正常黏膜未表现出任何病理变化。在肿瘤对照组（仅用7,12-二甲基苯并[a]蒽处理）中观察到由单核细胞、肥大细胞和一些多形核白细胞组成的炎性浸润，脱颗粒的多形核白细胞、肥大细胞和嗜酸性粒细胞占主导。值得注意的是，注射β-胡萝卜素脂质体后，并非所有退变发育异常或早期癌区域在黏膜附近都表现出密集的炎症反应。结果表明对实验性口腔癌消退有选择性无毒疗法。
