叶酸偶联纳米紫杉醇靶向治疗耐药卵巢癌的动物实验研究

Experimental Study of the Folic Acid-coupled Nano-paclitaxel Liposome in Targeting Treatment of Peritoneal Xenograft Model of Paclitaxel-resistant Ovarian Cancer

目的:研究腹腔注射叶酸偶联纳米紫杉醇(FA-N.P.)对耐药卵巢癌裸鼠的体内治疗效果,并探讨其最适给药方式。方法:建立裸鼠耐紫杉醇卵巢癌腹腔种植瘤模型,50只荷瘤鼠分5组,连续4周腹腔内分别注入空白载体(腹腔空白载体组)、紫杉醇(腹腔紫杉醇组)、纳米紫杉醇(腹腔N.P.组)、FA-N.P.(腹腔FA-N.P.组)及静脉注入FA-N.P.(静脉FA-N.P.组),比较其生存期及荷瘤量;电子显微镜及流式细胞仪定性和定量观察该药物对腹腔转移瘤的杀伤效果。结果:腹腔FA-N.P.组与其他4组比较,裸鼠生存期显著升高(P<0.05,P<0.01),瘤体数目(2.9±0.3个)明显降低(P<0.05,P<0.01)。腹腔FA-N.P.组瘤体内肿瘤细胞的凋亡率(44.6%±8.5%)明显高于其他4组(P<0.05)。与腹腔给药组比较,静脉FA-N.P.组肿瘤细胞的凋亡率降低(20.1%±6.2%,P<0.05)。结论:FA-N.P.药物靶向治疗耐药卵巢癌腹腔转移瘤有效,且腹腔给药效果优于静脉给药。

Objective： To research the effect and the mechanism of the folic acid-coupled nano-paclitaxel liposome（ FA-N. P.） in targeting treatment of paclitaxel-resistant ovarian cancer in vivo. Methods： 50 tumor-burdened nude mice were randomized divided into five groups： intraperitoneal（ i. p.） administration of blank vehicle,regular paclitaxel,nano-paclitaxel liposome（ N. P.）,i. p. administration of FA-N. P. and intravenous（ i. v.） administration of FA-N. P. for 4 consecutive weeks. The drug effects in vivo were examined by the survival,tumor nodule number and killing effect of peritoneal metastasis. Results： I. p. administration of FA-N. P. but not regular paclitaxel,N. P. or vehicle significantly prolonged the survival and reduced tumor nodule number（ 2. 9 ±0. 3） in BALB / c nude mice.FA-N. P. also markedly enhanced the percentage of apoptotic cells in peritoneal xenograft of paclitaxel-resistant ovarian cancer cells（ 44. 6% ±8. 5% vs. 3. 2% ±1. 1% for vehicle,22. 4% ±5. 9% for regular paclitaxel and 35. 2% ±7. 7% for nano-paclitaxel liposome,P〈0. 05）. However,i. v. administration of FA-N. P. at the same dose failed to induce apoptosis（ 20. 1% ±6. 2%,P〈0. 05） or inhibit tumor nodule number to the same extent as i. p. administration. Conclusions： Localized and targeted i. p. administration of FA-N. P. have better effects than i. v. administration in treating peritoneal xenograft model of drug-resistant ovarian cancer.