肿瘤坏死因子α对人肺腺癌细胞耐顺铂的影响

目的研究肿瘤坏死因子OL（TNF-α）对人肺腺癌细胞系A549／顺铂（DDP）耐DDP的逆转作用，探讨其与肺耐药相关蛋白（LRP）表达之间的关系。方法以MTT法检0n,0TNF-α与顺铂联用对A549／DDP细胞的细胞毒性作用，以免疫细胞化学方法检测A549／DDP细胞LRP的表达情况。结果250、1000U／mlTNF-α可使顺铂对A549／DDP细胞的IC50从7．12ng／L分别降至5．02、4．41ng／L，能够逆转A549／DDP对顺铂的耐药，逆转倍数分别为1．42、1．62。A549／DDP细胞LRP呈强阳性表达，250、1000U／mlTN-α与顺铂联用可以下调LRP表达，LRP阳性表达率分别为（60．14-4-6．54）％、（57．234-5．98）％，同无药组和顺铂组LRP表达率（79．63±4．78）％、（75．97±5．32）％比较，差异具有统计学意义（P均〈0．01）。结论TNF-α能够逆转A549／DDP对顺铂的耐药，其机制可能与下调LRP表达有关。

The effects of tumor necrosis factor-or on the cisplatin-resistant human lung adenocarcinoma cell lines A549/DDP

Objective To investigate the effects of tumor necrosis factor-α （TNF-α） on the resensitization of human lung cancer cell lines A549/DDP to cisplatin （DDP） and to explore the relationship between the expression of TNF-αand resistance-related protein （LRP） in lung tissue. Methods The cytotoxic effects of combinational treatment by TNF-α and cisplatin on A549/DDP were measured by MTF assay. The expression of LRP was assessed by immunocytochemistry methods. Results The IC50 of A549/DDP to cisplatin were decreased from 7. 12 ng/L to 5.02 ng/L,4. 41 ng/L respectively by 250 U/ml and 1000 U/ml TNF-α treatment （P 〈 0. 01 ）, with the sensitivity of A549/DDP to cisplatin increased by 1.42 and 1.62 fold respectively. LRP was overexpressed in A549/DDP cell. 250 U/ml or 1000 U/ml TNF-oL plus cisplatin treatment down-regulated the expression of LRP with the positive rates of （ 60. 14 ± 6. 54 ） % and （ 57.23 ± 5.98 ） % respectively, which were significantly lower than that of cisplatin alone treatment （75.97 ±5.32 ） % and control group （79. 63± 4. 78 ） % （ both P 〈 0. 01 ）. Conclusion Tumor necrosis factor-or can reverse the resistance of A549/DDP to cisplatin, which may be partially attributed to down-regulating LRP expression.