Bucur N, Mizuno M, Wakabayashi T, Yoshida J
Department of Neurosurgery, Nagoya University School of Medicine.
Neurol Med Chir (Tokyo). 1998 Aug;38(8):469-73; discussion 473-4. doi: 10.2176/nmc.38.469.
Intracellular production of human interferon-beta (HuIFN-beta) was enhanced in three glioma cell lines (U251-MG, U251-SP, and U251-NN) using modified superinduction with cationic liposomes containing polyinosilic:polycytidilic acid (polyI:polyC), initially given with cycloheximide, to decrease the toxicity due to polyI:polyC. Modified superinduction had a significantly (p < 0.02-0.0001) greater inhibitory effect on all three glioma cell lines, and less toxicity than superinduction. A pilot trial in experimental gliomas implanted into nude mice was also performed. Superinduction including intratumoral injection of cationic liposomes containing polyI:polyC resulted in growth inhibition of U251-NN tumors and eradication of U251-SP tumors. Weight gain in mice was not inhibited by modified superinduction. Cationic liposomes decreased drug toxicity, and may help to target tumor cells in the modified superinduction of endogenous HuIFN-beta production.
使用含有聚肌胞苷酸(polyI:polyC)的阳离子脂质体进行改良超诱导,最初联合放线菌酮给药,以降低polyI:polyC的毒性,从而在三种胶质瘤细胞系(U251-MG、U251-SP和U251-NN)中增强人β干扰素(HuIFN-β)的细胞内产生。改良超诱导对所有三种胶质瘤细胞系均具有显著(p < 0.02 - 0.0001)更强的抑制作用,且毒性低于超诱导。还在植入裸鼠的实验性胶质瘤中进行了一项初步试验。包括瘤内注射含有polyI:polyC的阳离子脂质体的超诱导导致U251-NN肿瘤生长受到抑制以及U251-SP肿瘤被根除。改良超诱导未抑制小鼠体重增加。阳离子脂质体降低了药物毒性,并且可能有助于在改良超诱导内源性HuIFN-β产生过程中靶向肿瘤细胞。