β-tubulin-Ⅲ基因的表达与长春瑞滨治疗非小细胞肺癌疗效关系的研究

The relationship between expression of β-tubulin-Ⅲ and therapeutic effect of vinorelbine on non-small cell lung cancer

目的:研究非小细胞肺癌(NSCLC)患者肿瘤组织中β-微管蛋白-Ⅲ(β-tubulin-Ⅲ)基因的表达与患者对长春碱类药物化疗敏感性的关系,为患者选择适当的药物治疗提供依据。方法:共入选35例NSCLC患者,随机分入长春瑞滨(NVB)联合顺铂(PDD)或卡铂(CBP)组成NP方案化疗组和吉西他滨(GEM)联合PDD或CBP组成GP方案组,观察两组对化疗的反应;同时以RT-PCR法检测患者病理组织中β-tubulin-ⅢmRNA的表达,以Westernblot检测β-tubulin-Ⅲ蛋白的含量。结果:NP组19例,GP组16例,两组患者临床特点无明显差别,对化疗总的有效率相似,在NP组内,有效10例,无效9例,有效患者的肿瘤组织中β-tubulin-Ⅲ mRNA测量值为4.8±1.9,而无效患者为15.8±8.0,两者有显著性差异(P<0.01);有效患者β-tubulin-Ⅲ蛋白的测量值为3.7±1.5,无效患者为13.5±6.2(P<0.01)。GP组7例无效,9例有效,有效与无效患者肿瘤组织中β-tubulin-Ⅲ mRNA和β-tubulin-Ⅲ蛋白表达均无显著性差异(P>0.05)。结论:NSCLC患者肿瘤组织中β-tubulin-Ⅲ基因的表达与患者对长春碱类药物的敏感性有关,β-tubulin-Ⅲ基因高表达,提示对长春碱类药物的敏感性低,宜换用其他药物治疗。

Objective： To study the relationship between expression of β-tubulin-III gene in non-small cell lung cancer （NSCLC） biopsy and its sensitivity to vinblastine alkaloid, which would provide a basis of the proper medicine choice for the patients. Methods： NSCLC patients accepted chemotherapy of vinorelbine （ NVB ） ± cisplatin （ PDD ）/carboplatin （CBP） or gemcitabine （GEM） ± PDD/CBP randomly, and the responses were recorded. RT-PCR technology was used to examine the mRNA of β-tubulin-III gene, and western blot was used to investigate β-tubulin-III protein at the same time. Results：Nineteen patients were treated with NP regimen and 16 with GP regimen. There were no differences of the clinical characteristics and the therapy responses between the two group patients. In NP group, 10 patients had responses to the cytotoxic drugs. The β-tubulin-III mRNA level of the former was 4. 8 ± 1.9 ,and 15.8 ± 8.0 of the latter, which showed a statistically significant difference（ P 〈 0. 01 ）. The translation level of β-tubulin- Ill protein in the former was 3. 7 ± 1.5 while 1.5 ±6. 2 in the latter（P 〈0. 01 ）. In the GP group, 9 patients showed responses to the chemotherapy, but there were no significant difference between these patients neither in β-tubulin-III mRNA （ P 〉 0. 05 ） nor in β-tubulin-III protein（ P 〉 0. 05 ）. Conclusion：The expression of β-tubulin-III gene in NSCLC biopsy had relationship with the sensitivity of the patient to vinorelbine. Patients with high level of β-tubulin-III gene expression would have poor responses to this cytotoxic drugs.