Paclitaxel nanoparticle inhibits growth of ovarian cancer xenografts and enhances lymphatic targeting
Paclitaxel nanoparticle inhibits growth of ovarian cancer xenografts and enhances lymphatic targeting
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DOI：
10.1007/s00280-006-0256-z
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发表时间：
2007-02-01
影响因子：
3
通讯作者：
Xu, Congjian
中科院分区：
文献类型：
--
作者：
Lu, Hongxia;Li, Bin;Xu, Congjian
目的：卵巢癌是所有妇科癌症中死亡率最高的。抗肿瘤药紫杉醇已被证明是有效的治疗卵巢癌。我们的研究是开发紫杉醇的聚合物给药系统，并确定紫杉醇纳米粒是否可以抑制卵巢癌Fisher 344（F344）大鼠移植瘤的生长。本研究探讨紫杉醇纳米粒对卵巢癌大鼠的作用机制。研究方法：超声乳化法制备紫杉醇纳米粒; MTT法检测紫杉醇纳米粒的体外细胞毒活性; F344大鼠腹腔注射大鼠卵巢癌细胞。通过测量肿瘤重量和腹水体积评价紫杉醇纳米粒的体内抗肿瘤作用。手术结束后处死大鼠，切除肿瘤并进行PCNA染色、组织末端脱氧核苷酸转移酶介导的dUTP缺口标记分析和RT-PCR以评估PLA诱导的肿瘤增殖和凋亡变化以及癌转移相关基因表达。通过高效液相色谱法测定血浆、盆腔淋巴结、肝脏和心脏中的紫杉醇浓度。结果：紫杉醇纳米粒与紫杉醇（Cremophor）体外细胞毒活性相当。紫杉醇纳米粒能显著降低大鼠移植瘤的瘤重和腹水量，并诱导肿瘤细胞凋亡。PLA还抑制细胞增殖和基质金属蛋白酶9 mRNA的表达。腹膜内给药后48 h，PLA治疗动物盆腔淋巴结的紫杉醇浓度是游离PTX治疗动物的20倍。结论：紫杉醇纳米粒腹腔给药能显著抑制雌性F344大鼠腹腔内卵巢癌的进展。紫杉醇纳米粒是安全的和淋巴靶向的。
Objectives: Ovarian cancer has the highest mortality of all the gynecologic cancers. The antitumor agent paclitaxel has been proved to be efficient in the treatment of ovarian cancer. Our study is to develop a polymeric drug delivery system for paclitaxel and determine whether paclitaxel nanoparticle can inhibit growth of ovarian carcinoma xenografts in Fisher344 (F344) rats by intraperitoneal administration. The mechanism of paclitaxel nanoparticles in rats bearing ovarian cancer has been investigated in this study. Methods: Synthesize paclitaxel loading nanoparticle (PLA) by ultrasonic emulsification; MTT analysis identified cytotoxic activity of paclitaxel nanoparticle in vitro; rat ovarian carcinoma cells were injected into the peritoneal cavity of F344 rats. The antitumor effect of paclitaxel nanoparticle in vivo has been evaluated by measuring tumor weight and ascite volume. At the end of the procedure rats were sacrificed; tumors were excised and processed for PCNA staining, tissue terminal deoxynucleotide transferase-mediated dUTP nick and labeling assay and RT-PCR to evaluate the proliferative and apoptotic changes and cancer transfer-related gene expression induced by PLA. Paclitaxel concentration in plasma, pelvic lymph nodes, liver, and heart were determined by high-performance liquid chromatography. Results: Paclitaxel nanoparticle and PTX ( Cremophor) showed equivalent cytotoxic activity in vitro. In rats implanted carcinoma cells, paclitaxel nanoparticles significantly reduced tumor weight and ascites volume, and induced apoptosis of tumor cells. PLA also inhibited cell proliferation and matrix metalloproteinase 9 mRNA expression. The paclitaxel concentration of pelvic lymph nodes in PLA treated animals was 20-fold higher than that of free PTX treated animals at 48 h after intraperitoneal administration. Conclusion: The intraperitoneal administration of paclitaxel nanoparticle can significantly inhibit the progression of ovarian carcinoma in peritoneal cavity of female F344 rat. The paclitaxel nanoparticle is safe and lymphatic targeting.