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目的观察肿瘤间质内应用替莫唑胺缓释剂(P-TMZ)对人脑胶质瘤的抑瘤效应。方法先以MTT法测定P-TMZ对SHG-44胶质瘤细胞的抑瘤效应,加药96h后检测不同药物浓度在570nm处的OD值,计算其IC50;再将SHG-44细胞接种于NC系裸小鼠右腋皮下,待肿瘤生长至体积约100mm3时,将荷瘤鼠随机分为P-TMZ组、替莫唑胺(temozolomide,TMZ)组、卡莫斯汀(BCNU)组和不载药微球(P-0)组,然后将P-TMZ(500mg/kg)、TMZ(50mg/kg)、BCNU(40mg/kg)和P-0(500mg/kg)以DMEM培养液混悬至终体积150μl,经皮多点穿刺缓慢注入相应组肿瘤间质内,每周测量皮下肿瘤大小2次。结果P-TMZ、TMZ和BCNU对SHG-44胶质瘤细胞的体外抑瘤效果明显,三者的IC50均<10μg/ml;与P-0组比较,差异均具有统计学意义(P<0.01)。在体内抑瘤实验中,P-TMZ、BCNU、TMZ抑瘤率均明显高于P-0(P<0.01)。P-TMZ和BCNU的抑瘤效应优于TMZ组(P<0.05)。结论P-TMZ保留了TMZ的抑瘤活性,兼具高稳定性和长时程药物作用时间等药代动力学特征,为胶质瘤病人肿瘤残腔内间质化疗提供了新的治疗选择。
Objective To observe the antitumor effect of temozolomide sustained-release agent (P-TMZ) on human glioma in tumor stroma. Methods The anti-tumor effect of P-TMZ on SHG-44 glioma cells was determined by MTT method. The OD values of different drug concentrations at 570 nm were measured 96 h after drug addition, and the IC50 was calculated. SHG-44 cells were seeded on NC The mice were randomly divided into P-TMZ group, temozolomide (TMZ) group, carmustine (BCNU) group and drug-free micro-drug P-TMZ (500 mg / kg), TMZ (50 mg / kg), BCNU (40 mg / kg) and P-0 (500 mg / kg) were suspended in DMEM medium to a final volume 150μl, percutaneous multi-point puncture slowly injected into the corresponding group of tumor stroma, measuring subcutaneous tumor size twice a week. Results The inhibitory effect of P-TMZ, TMZ and BCNU on SHG-44 glioma cells in vitro was significant, with IC50 of <10μg / ml. Compared with P-0 group, the difference was statistically significant (P <0.01 ). In vivo anti-tumor experiments, P-TMZ, BCNU, TMZ tumor inhibition rates were significantly higher than P-0 (P <0.01). The antitumor effect of P-TMZ and BCNU was better than TMZ group (P <0.05). Conclusions P-TMZ preserves the anti-tumor activity of TMZ and possesses the characteristics of high pharmacokinetics such as high stability and long-term drug action time. It provides a new therapeutic option for the treatment of interstitial chemotherapy in tumor residual tumor of glioma patients.