Dinney C P, Tanguay S, Bucana C D, Eve B Y, Fidler I J
Department of Cell Biology, University of Texas-M.D. Anderson Cancer Center, Houston 77030, USA.
J Interferon Cytokine Res. 1995 Jun;15(6):585-92.
The present study evaluated the in vivo activity of synthetic lipophilic muramyl tripeptide phosphatidylethanolamine (MTP-PE) when encapsulated into liposomes (phosphatidylcholine-phosphatidylserine, 7:3 molar ratio) and administered intravesically to athymic nude mice with human transitional cell carcinoma 253J-V cells growing in their bladder. Intravesical liposome-MTP-PE was effective in eradicating the human tumors implanted orthotopically in nude mice. Following therapy, activated macrophages were found in the bladders of liposome-MTP-PE-treated mice but not in control mice. In vitro activation of murine macrophages with liposome-MTP-PE increased their cytotoxicity against the 253J-V cell line used in these experiments. This effect was enhanced by cotreatment with interferon-gamma (IFN-gamma). Furthermore, cotreatment of macrophages with both liposome-MTP-PE and IFN-gamma resulted in the secretion of both tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Liposome-encapsulated MTP-PE shows promise as an effective therapeutic agent for bladder carcinoma.
本研究评估了合成的亲脂性胞壁酰三肽磷脂酰乙醇胺（MTP-PE）包裹于脂质体（磷脂酰胆碱-磷脂酰丝氨酸，摩尔比7:3）中并膀胱内给药于膀胱内生长有人移行细胞癌253J-V细胞的无胸腺裸鼠时的体内活性。膀胱内给予脂质体-MTP-PE可有效根除原位植入裸鼠体内的人肿瘤。治疗后，在脂质体-MTP-PE治疗的小鼠膀胱中发现了活化的巨噬细胞，而对照小鼠中未发现。用脂质体-MTP-PE体外激活小鼠巨噬细胞可增强其对这些实验中所用253J-V细胞系的细胞毒性。用干扰素-γ（IFN-γ）共同处理可增强此效应。此外，用脂质体-MTP-PE和IFN-γ共同处理巨噬细胞可导致肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）的分泌。脂质体包裹的MTP-PE有望成为一种有效的膀胱癌治疗药物。
