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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。
OBJECTIVE: To observe the effect of OALA in situ on the biological activity of 5-Fu, a chemotherapeutic drug of tumor, to provide experimental basis for 5-Fu loading. Methods: The effects of different concentrations of OALA on the proliferation of human lung adenocarcinoma (A549), breast cancer (MCF-7) and colon cancer (LOVO) cells were evaluated by MTT assay. The cytotoxicity of OALA on 5-Fu in vitro The effects of different doses of 5-Fu and intravenous injection of OALA solution on the mortality of animals were observed and compared with those of 5-Fu injection group. Ehrlich ascites carcinoma (EAC) mice As a model to observe the effect of certain dose of 5-Fu and its combination with OALA on tumor growth in mice. The tumor growth inhibition rate was taken as the evaluation index. Results: With the increase of OALA concentration, the inhibitory effect on the proliferation of A549, MCF-7 and LOVO cells gradually increased, with a clear dose-effect relationship; 30μg.mL-1 OALA combined with 5-Fu does not increase or decrease the drug OALA could reduce the mortality of animals in 5-Fu medium and high dose groups (P <0.05), but had no effect on the mortality of animals in low dose group. OALA alone could reduce the 5-Fu The antitumor activity of EAC in mice (P <0.05), but no significant change in tumor inhibition rate was observed in multiple combination groups compared with 5-Fu multiple administration groups. Conclusion: OALA has a certain impact on the biological activity of 5-Fu.