Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
College of Biology, Hunan University, Changsha 410082, China.
Cancer Biol Med. 2020 Feb 15;17(1):237-250. doi: 10.20892/j.issn.2095-3941.2019.0169.
Cisplatin (CDDP) is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors, including ovarian cancer. However, adverse side effects and acquired drug resistance are observed in the clinical application of CDDP. Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem. In this study, 3D printing technology was used to prepare a CDDP-poly (lactic-co-glycolic acid) (CDDP-PLGA) polymer compound stent, and its physicochemical properties and cytotoxicity were evaluated both and . The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice, whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection. Compared with the control group, CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein ( < 0.01; < 0.01) and decreased vascular endothelial growth factor mRNA ( < 0.05) and protein levels ( < 0.01), however, CDDP-PLGA significantly decreased the mRNA and protein levels of p-glycoprotein ( < 0.01; < 0.01) and vascular endothelial growth factor ( < 0.01; < 0.01), which are associated with chemoresistance, in subcutaneous tumor tissue. Immunohistochemistry assay results revealed that, in the CDDP-PLGA group, the staining of the proliferation-related genes Ki67 and PCNA were lightly, and the apoptosis-related gene caspase-3 stained deeply. PLGA biomaterials loaded with CDDP, as compared with the same amount of free CDDP, showed good efficacy in terms of cytotoxicity, as evidenced by changes in apoptosis. Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis, and improve the therapeutic effect. This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.
顺铂（CDDP）是一种广泛应用于治疗多种肿瘤（包括卵巢癌）的基本化疗药物。然而，在 CDDP 的临床应用中观察到不良反应和获得性耐药性。确定一种可以减轻副作用和降低耐药性的给药方式已成为解决这一问题的有前途的策略。 在这项研究中，使用 3D 打印技术制备了 CDDP-聚（乳酸-共-羟基乙酸）（CDDP-PLGA）聚合物复合支架，并对其理化性质和细胞毒性进行了评价。 CDDP-PLGA 支架对细胞增殖和凋亡有明显影响，明显缩小了裸鼠皮下肿瘤的体积，而全身副作用与腹腔注射 CDDP 相比较轻。与对照组相比，CDDP-PLGA 显著增加了 p-糖蛋白的 mRNA 和蛋白水平（<0.01；<0.01），降低了血管内皮生长因子的 mRNA（<0.05）和蛋白水平（<0.01），但 CDDP-PLGA 显著降低了 p-糖蛋白的 mRNA 和蛋白水平（<0.01；<0.01）和血管内皮生长因子（<0.01；<0.01），这与化疗耐药性有关，在皮下肿瘤组织中。免疫组织化学检测结果显示，在 CDDP-PLGA 组，增殖相关基因 Ki67 和 PCNA 的染色较轻，凋亡相关基因 caspase-3 染色较深。与等量游离 CDDP 相比，载有 CDDP 的 PLGA 生物材料在细胞毒性方面表现出良好的疗效，这表现在凋亡的变化上。持续局部释放 CDDP 可以降低药物的全身副作用和耐药性和血管生成的发生，提高治疗效果。这种新方法可能是上皮性卵巢癌局部治疗的有效策略。
