摘要
目的探讨A549肺腺癌多细胞球体放射抗拒细胞的化疗药物敏感性。方法放射抗拒细胞为6MV高能X线照射25Gy后的第10代再增殖细胞,对照组为A549亲代细胞和MCF7长春新碱耐药(MCF7VCR)细胞。6种化疗药物分别为顺铂(DDP)、长春花碱酰胺(VDS)、5氟尿嘧啶(5FU)、羟基喜树碱(HCP)、丝裂霉素(MMC)和阿霉素(ADM),异搏定(VPL)作为耐药逆转剂。MTT比较药敏试验效果,RT PCR检测mdr1和MRP耐药基因表达。结果A549亲代和放射抗拒细胞对DDP耐药,对VDS、5FU、HCP、MMC和ADM敏感,VPL的抑制率分别为98%和25%(P<0.001)。未加药组A549亲代细胞的A值为放射抗拒细胞的2倍(P<0.001)。MCF7VCR细胞对DDP和MMC耐药,对VDS、5FU、HCP和ADM较敏感,VPL的抑制率80%。A549所有细胞的mdr1β2MG为0,MRPβ2MG为0.7左右,MCF7VCR分别为35和4.36。结论A549放射抗拒细胞的化疗药物敏感性无明显变化,对VPL的敏感性减低不能以mdr1和MRP耐药基因的表达水平来解释,可能与某种膜蛋白的变化,以及细胞增殖能力减低有关。与化疗引起的多药耐药不同,对于放射抗拒细胞,VPL可能不是一个理想的耐药逆转剂,应寻求新的生物制剂联合化疗药物治疗放射抗拒复发肿瘤。
Objective To investigate the chemosensitivity of irradiated resistant cells of muhicellular spheroids in A549 lung adenocarcinoma. Methods The A549 irradiated resistant cells were the 10th regrowth generations after irradiated with 25 Gy of 6 MV X-ray, with the control groups were A549 parent cells and MCFT/ VCR resistant cells. The 6 kinds of chemotherapeutic drugs were DDP, VDS, 5-FU, HCP, MMC and ADM respectively, with verapamil （VPL） as reverse agent, The treatment effect was compared with MTT assay, and the multidrug resistant gene expressions of mdrl and MRP were measured with RT-PCR method. Results A549 cells and irradiated resistant cells were resistant to DDP, but sensitivity to VDS,5-FU, HCP, MMC and ADM. The inhibitory rates of VPL to the above two cells were 98% and 25% respectively（ P 〈 0.001 ）, The A value of the control A549 cells was 2 times of irradiated resistant cells （ P 〈 0.001 ）. MCFT/VCR cells were resistant to DDP and MMC, but slight sensitivity to VDS,5-FU, HCP and ADM, with 80% of inhibitory rate to VPL, mdrl/β2 -MG and MRP/β2-MG of all A549 cells were about 0 and 0. 7 respectively, and those of MCF7/VCR ceils were 35 and 4,36. Conclusion The chemosensitivity of A549 irradiated resistant cells had not changed markedly, the decreased sensitivity to VPL could not be explained by the gene expression of mdrl and MRP. It is conferred that some kinds of changes in the cell membrane and decreased regrowth ability to result in resistance. Unlike muhidrug resistance induced by chemotherapy, VPL may be not an ideal reverser to irradiated resistant cells, The new kinds of biological preparation should be seeked to combine chemotherapy to treat recurring tumor with irradiated resistance.
出处
《中华放射医学与防护杂志》
CAS
CSCD
北大核心
2006年第2期155-158,共4页
Chinese Journal of Radiological Medicine and Protection
基金
国家自然科学基金资助项目(30470497)
关键词
肺腺癌
多细胞球体
放射
抗拒
化疗药物敏感性
Lung adenocarcinoma
Multicellular spheroids
Irradiation
resistant
Chemosensitivity
