麝香酮对肺癌细胞的顺铂耐药和小鼠体内的肿瘤生长的作用

The effect of Muscone on lung cancer cells resistance to cisplatin and tumor growth in mice

目的:研究麝香酮对肺癌A549/DDP耐药细胞增殖和顺铂耐药的功能影响以及分子机制,并探究其在体内对肿瘤生长的作用。方法:将肺癌A549/DDP耐药细胞分为对照组(0μmol/L组)、4μmol/L组、8μmol/L组、16μmol/L组,细胞培养贴壁后分别加入0μmol/L、4μmol/L、8μmol/L、16μmol/L的麝香酮培养24 h后,CCK-8法检测麝香酮对肺癌A549/DDP耐药细胞增殖的影响;Western blotting检测耐药相关蛋白MRP-1和P-gp以及NF-κB信号通路蛋白的表达水平;30只小鼠随机分为对照组、生理盐水组及麝香酮组,采用皮下注射A549/DDP耐药细胞悬液法建立肺癌移植瘤模型小鼠,麝香通组给予麝香酮(16 mg/kg)生理盐水组给予生理盐水,对照组不干预,1次/d,连续给药28 d,测量各组小鼠瘤块体积及重量。结果:与0μmol/L组相比,麝香酮各剂量组能够显著抑制肺癌A549/DDP耐药细胞的增殖、耐药相关蛋白MRP-1和P-gp的蛋白表达水平以及NF-κB通路相关蛋白的蛋白表达水平,包括p50、p52和p65,并呈现剂量依赖性(均P<0.05);与对照组相比,麝香酮显著抑制小鼠体内的肿瘤生长,包括肿瘤体积和肿瘤重量(均P<0.05)。结论:麝香酮能够显著抑制肺癌A549/DDP耐药细胞的增殖和顺铂耐药,并抑制小鼠体内的肿瘤生长,其机制可能与调节NF-κB通路有关。

Objective:To study the function and molecular mechanism of Muscone on proliferation and cisplatin resistance of lung cancer cell line A549/DDPand its effect on tumor growth in vivo.Methods:Lung cancer A549/DDP cells were divided into control group(0μmol/L group),4μmol/L group,8μmol/L group and 16μmol/L group.After being cultured with 0μmol/L,4μmol/L,8μmol/L and 16μmol/L Muscone for 24 hours,the effect of muscone on the proliferation of A549/DDP cells was detected by CCK-8.The expression of MRP-1 and P-gp and NF-κB signal pathway proteins were detected byWestern blotting.Thirty mice were randomly divided into control group,normal saline group and Muscone(16 mg/kg)group.Lung cancer transplanted tumor mice models were established by subcutaneous injection of A549/DDP cell suspension.The tumor volume and weight of mice were measured.Results:Compared with the control group,Muscone significantly inhibited the proliferation of A549/DDP cells and down-regulated the expressions of MRP-1,P-gp and NF-κB signaling pathway proteins such as p50,p52 and p65 in a dose-dependent manner(P<0.05).Muscone significantly inhibited the growth of tumor(including tumor volume and tumor weight)in mice(P<0.05).Conclusion:Muscone can not only inhibit the proliferation and cisplatin resistance of lung cancer cell line A549/DDPbutalso mitigate tumor growth in mice.The mechanism may be related to the regulation of NF-κB pathway.