摘要
背景和目的糖调节蛋白78(GRP78)在乳腺癌细胞中表达增高并与其对化疗药物的耐药性有关,而非小细胞肺癌(NSCLC)中GRP78的表达与其对化疗药物的耐药性是否相关,研究较少。本研究拟探讨NSCLC对8种化疗药物的体外敏感性与GRP78表达的相关性。方法采用四噻唑蓝(MTT)法对52例手术切除的新鲜NSCLC组织进行8种化疗药物体外敏感性检测;采用免疫组织化学方法检测其GRP78的表达水平。采用Spearman相关分析对NSCLC的耐药性与GRP78表达的相关性进行分析。结果52例NSCLC对紫杉醇(PTX)、阿霉素(ADM)、卡铂(CBP)、拓扑替康(TPT)、长春瑞滨(NVB)、长春新碱(VCR)、顺铂(DDP)和鬼臼乙叉苷(VP-16)8种化疗药物的耐药率分别为42.31%、57.69%、63.46%、65.38%、67.31%、73.08%、78.85%、90.38%,其中14例表现为完全耐药。GRP78的表达水平随着肺癌恶性程度的提高而增加,且其高表达与肺癌细胞对VP-16、ADM、VCR和TPT的耐药具有相关性(P<0.05)。结论MTT法体外化疗药物敏感性实验对NSCLC的治疗具有一定的指导作用,GRP78对判定NSCLC的恶性程度及其耐药性具有一定的参考意义。
Background and objective The expressive level of glucose-regulated protein 78 （GRP78） is elevated and correlated with resistance of chemotherapy drugs in breast cancer cell. However, little is known about the relationship between its expression and drug resistance in non-small cell lung cancer （NSCLC）. The aim of this study was to explore the relationship between drug resistance and the expression of GRP78 in NSCLC. Methods Drug sensitivity test was used to detect the resistance to 8 chemotherapy drugs in 52 NSCLC fresh surgical samples by methylthiazoletrazolium （MTT）, and expression of GRP78 was detected by immunohistochemistry method. Spearman correlation assay was used to investigate the correlation between the GRP78 expression and drug resistance. Results The resistance rates to paclitaxel （PTX）, adriamycin （ADM）, carboplatin （CBP）, topotecan （TPT）, navelbine （NVB）, vincristine （VCR）, cisplatin （DDP） and etoposide （VP-16） of the 52 samples were 42. 31%, 57. 69%, 63. 46%, 65. 38%, 67. 31%, 73. 08%, 78.85 %, 90.38%, respectively. Fourteen cases showed the complete resistance to the total 8 chemotherapy drugs. Furthermore, the expression of GRP78 was stronger in poorly differentiated cancer as compared with the well and moderately differentiated cancer （P〈0.05）, so as in stage Ⅱ and Ⅲ cancer than in stage Ⅰ cancer （P〈0.05）. Spearman correlation assay showed that there was a correlation between the chemotherapeutics resistance to ADM, VP-16, VCR, TPT and the expression of GRP78 in NSCLC （P〈0.05）. Conclusion It is feasible to detect the drug sensitivity to chemotherapy for tumor cells by MTT method. The results of chemo- sensitivity assay in vitro are indicative of clinical drug administration in NSCLC. The detection of GRP78 is also indicative of the resistance to chemotherapy drugs and the differentiation and the clinical stage in NSCLC.
出处
《中国肺癌杂志》
CAS
2006年第6期483-487,共5页
Chinese Journal of Lung Cancer
基金
国家自然科学基金(No.30470464)
辽宁省科技厅(No.20022125)
辽宁省教育厅(No.20223274)资助~~
关键词
非小细胞肺癌
糖调节蛋白78
四噻唑蓝
体外药敏实验
耐药
Non-small cell lung cancer Glucose-regulated protein 78 Methylthiazoletrazolium Chemosensitivity in vitro Resistance
