原位凝胶材料OALA对氟尿嘧啶生物活性影响

目的:观察原位凝胶材料OALA对肿瘤化疗药物氟尿嘧啶(5-Fu)生物活性的影响,从而为其负载5-Fu提供实验依据。方法:采用MTT法评价不同浓度的OALA对人肺腺癌(A549)、乳腺癌(MCF-7)和结肠癌(LOVO)细胞增殖能力的影响;采用MTT法评价OALA对5-Fu体外细胞毒性的影响;给予不同剂量的5-Fu作用下及以OALA溶液静脉注射干预,观察动物的死亡率,并与单纯注射5-Fu组动物死亡率进行比较;以艾氏腹水癌(EAC)小鼠为模型,观察一定剂量的5-Fu及其联用OALA对小鼠肿瘤生长状况的影响,采用肿瘤生长抑制率作为其评价指标。结果:随着OALA浓度的增加其对A549、MCF-7及LOVO细胞的增殖抑制作用逐渐增强,具有明确的量效关系;30μg.mL-1的OALA合用5-Fu后不会增加或降低药物本身的细胞毒性;OALA能够降低5-Fu中、高剂量组动物的死亡率(P<0.05),但对低剂量组动物的死亡率无明显影响;OALA单次给药能够降低5-Fu对小鼠EAC的抗肿瘤活性(P<0.05),而多次合用药组与5-Fu多次给药组相比抑瘤率无明显改变。结论:OALA对5-Fu的生物活性有一定影响。

The impact of in situ gel OALA on bioactivity of 5-Fu

OBJECTIVE To investigate the impact of in situ gel OALA on the biological activity of chemotherapeutic drug 5-Fu,and provide the experimental basis for OALA to load 5-Fu.METHODS The effects of OALA in different concentration on the proliferation of A549,MCF-7 and LOVO cells were assayed by using MTT method;the cytotoxicity of OALA was evaluated by MTT.The animal death rate were determined at the different dose of 5-Fu and OALA solution via injection and compared with that of the group with single 5-Fu intraperitoneal administration;the impact of different doses of 5-Fu and 5-Fu combined with OALA on tumor growth in EAC tumor-bearing mice and evaluated by tumor growth inhibition rate.RESULTS The inhibitiory effects on A549,MCF-7 and LOVO cells proliferation was increased,as the concentration of OALA increased,showing dose-effect relationship obviously.5-Fu co-administered with OALA at the concentration of 30 μg·mL-1 did not increase or decrease the cytotoxicity of 5-Fu itself;the animal mortality increased in middle and high dose of 5-Fu group,but had no effect in low dose of 5-Fu,which were co-administered with OALA.The anti-tumour activity of 5-Fu in EAC mice was decreased by injection of OALA once,but had no different by multiple dosing of OALA.CONCLUSION OALA had influence on bioactivity of 5-Fu.