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目的探讨超声介导下蓖麻毒素缓释剂瘤体内注射对荷紫杉醇耐药人卵巢癌裸鼠皮下移植瘤增殖的抑制作用。方法采用开环聚合法合成聚乳酸羟基乙酸-聚乙二醇-聚乳酸羟基乙酸(PLGA-PEG-PLGA),并制成蓖麻毒素温敏型凝胶、紫杉醇凝胶。采用浓度梯度递增法建立人卵巢癌耐药细胞株A2780/PTX,建立荷紫杉醇耐药人卵巢癌细胞的裸鼠皮下移植瘤模型,随机分为模型组、空白凝胶组、紫杉醇组、紫杉醇凝胶组、蓖麻毒素组、蓖麻毒素凝胶组。在超声引导下,对荷紫杉醇耐药人卵巢癌细胞的裸鼠瘤灶分别注射不同药物,空白凝胶组注射空白凝胶(0.2 mL),紫杉醇组注射紫杉醇(20 mg/kg),紫杉醇凝胶组注射紫杉醇凝胶(20 mg/kg,0.2 mL),蓖麻毒素组注射蓖麻毒素(10μg/kg),蓖麻毒素凝胶组注射蓖麻毒素温敏型凝胶(10μg/kg,0.2 mL),定时超声测量肿瘤体积的变化,计算肿瘤生长抑制率。结果 A2780/PTX细胞株对紫杉醇的耐药指数为12.4。在超声介导下,瘤体内注射蓖麻毒素温敏型凝胶明显抑制荷耐药人卵巢癌裸鼠皮下移植瘤的增殖,与模型组比较,给药后4周肿瘤质量明显缩小(P<0.01),肿瘤生长抑制率达56.5%,明显高于紫杉醇组的16.1%、紫杉醇凝胶组的31.6%及蓖麻毒素组的28.9%。结论超声介导蓖麻毒素温敏型凝胶可有效抑制耐药人卵巢癌增殖,具有潜在的临床应用价值。
Objective To investigate the inhibitory effect of ultrasound-mediated ricin-releasing sustained-release agent on the proliferation of subcutaneous xenografts in nude mice bearing drug-resistant human ovarian cancer. Methods Poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) was synthesized by ring-opening polymerization and was used as ricin gels and paclitaxel gels. Human esophageal cancer cell line A2780 / PTX was established by increasing the concentration gradient. The nude mouse xenografts model of drug-resistant human ovarian cancer cells was established and divided into model group, blank gel group, paclitaxel group, paclitaxel coagulation group Glue group, ricin group, ricin gel group. Under the guidance of ultrasound, nude mice bearing taxol-resistant human ovarian cancer cells were injected with different drugs respectively. Blank gel was injected with blank gel (0.2 mL), paclitaxel was injected with paclitaxel (20 mg / kg), paclitaxel The mice were injected with paclitaxel gel (20 mg / kg, 0.2 mL), ricin toxin (10 μg / kg), ricin toxin gels (10 μg / kg, 0.2 mL). Tumor ultrasound was used to measure the change of tumor volume and the tumor growth inhibition rate was calculated. Results The resistance index of A2780 / PTX cell line to paclitaxel was 12.4. Ultrasound-mediated injection of ricin-sensitive gels significantly inhibited the proliferation of nude mice bearing drug-resistant human ovarian cancer xenografts in nude mice. Compared with the model group, the tumor mass was significantly reduced 4 weeks after administration (P < 0.01). The rate of tumor growth inhibition was 56.5%, which was significantly higher than 16.1% of paclitaxel group, 31.6% of paclitaxel gel group and 28.9% of ricin group. Conclusion Ultrasound-mediated ricin-sensitive gels can effectively inhibit the proliferation of drug-resistant human ovarian cancer and have potential clinical value.