摘要
目的观察原位凝胶材料OALA对肿瘤化疗药物顺铂生物活性的影响,从而为其负载DDP提供实验依据。方法采用MTT法评价不同浓度的OALA凝胶材料对肿瘤细胞(A549人肺癌细胞、MCF-7人乳腺癌细胞、LOVO人结肠癌细胞)增殖能力的影响;采用MTT法评价OALA凝胶材料对DDP体外细胞毒性的影响;采在不同剂量的DDP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DDP组动物死亡率进行比较;建立以EAC荷瘤小鼠模型,观察一定剂量的DDP及其联用OALA凝胶材料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的OALA合用DDP后不会增加或降低药物本身的细胞毒性;OALA能够增加DDP低剂量组动物的死亡率,但对DDP中、高剂量组动物的死亡率无明显影响;OALA对DDP本身的抗肿瘤活性无影响。结论 OALA对顺铂的生物活性基本没有影响。
【Objective】 To observe the impact of in situ gel OALA on biological activity of chemotherapeutic drug DDP,and provide the experimental basis for OALA to load DDP.【Methods】 ①The cytotoxicity of OALA in vitro： SRB method was used to evaluate the effects of OALA in different concentrations on the proliferation of tumor cells（A549 lung cancer cells,MCF-7 breast cancer cells,LOVO colon cells）,then determine the non-toxic concentration of OALA in these cells in vitro.②The impact of OALA on the toxicity of DDP in vitro： Firstly pre-test to determine the IC50 of chemotherapeutic drug DDP action on A549,MCF-7,LOVO and L929 cell lines respectively,then MTT method was used to evaluate the impact of OALA on cytotoxicity of DDP in vitro.③The impact of OALA on the toxicity of DDP in vivo： Firstly pre-test to determine the lethal dose of chemotherapeutic drugs DDP action on KM mice,then to intervene under different lethal dose injecting OALA intravenously,to compare mortality with the group of single DDP administrating intraperitoneally.④The impact of OALA on the in vivo antitumor activity of DDP： The EAC tumor-bearing mice were used as the experimental model to observe the impact of different doses of DDP and DDP combined with OALA on tumor growth in mice,then tumor growth inhibition rate was taken as its index.【Results】 ①The results of cytotoxicity in vitro showed that OALA-30 μg/mL had no influence on the proliferation of A549,MCF-7 and LOVO cells.②OALA-30 μg/mL was non-toxic or the inhibition was weak for A549,MCF-7,LOVO and L929 cell lines,OALA combined with three chemotherapeutic drugs would not increase or decrease the cytotoxicity of drug itself.③OALA could increase the animal mortality in DDP low dose group,but had no significant effect on the animal mortality of DDP high and median.④OALA had no effect on the anti-tumor activity of DDP.【Conclusion】 In vitro,OALA had no effect on the cytotoxicity of DDP;In vivo,OALA could differently interfere with the toxicity of DDP,but ha
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2013年第13期1-5,共5页
China Journal of Modern Medicine
基金
国家863计划课题(No:2009AA03Z313)
