Mansoori Maryam, Golalipour Masoud, Alizadeh Shahriar, Jahangirerad Ataollah, Khandozi Seyed Reza, Fakharai Habibollah, Shahbazi Majid
Medical Cellular and Molecular Research Center Talghani Children Hospital of Golestan University of Medical Sciences, Bolv Janbazan, Iran E-mail :
Asian Pac J Cancer Prev. 2015;16(18):8467-71. doi: 10.7314/apjcp.2015.16.18.8467.
One of the major mechanisms for drug resistance is associated with altered anticancer drug transport, mediated by the human-adenosine triphosphate binding cassette (ABC) transporter superfamily proteins. The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy. In our study we have studied the possibility that structural single-nucleotide polymorphisms (SNP) are the mechanism of ABCB1 overexpression.
A total of 101 gastric cancer multidrug resistant cases and 100 controls were genotyped with sequence-specific primed PCR (SSP-PCR). Gene expression was evaluated for 70 multidrug resistant cases and 54 controls by real time PCR. The correlation between the two groups was based on secondary structures of RNA predicted by bioinformatics tool.
The results of genotyping showed that among 3 studied SNPs, rs28381943 and rs2032586 had significant differences between patient and control groups but there were no differences in the two groups for C3435T. The results of real time PCR showed over-expression of ABCB1 when we compared our data with each of the genotypes in average mode. Prediction of secondary structures in the existence of 2 related SNPs (rs28381943 and rs2032586) showed that the amount of ΔG for original mRNA is higher than the amount of ΔG for the two mentioned SNPs.
We have observed that 2 of our studied SNPs (rs283821943 and rs2032586) may elevate the expression of ABCB1 gene, through increase in mRNA stability, while this was not the case for C3435T.
耐药的主要机制之一与抗癌药物转运改变有关，这是由人类三磷酸腺苷结合盒（ABC）转运蛋白超家族介导的。多药耐药癌细胞中三磷酸腺苷结合盒亚家族B成员1（ABCB1）的过表达是化疗的严重障碍。在我们的研究中，我们研究了结构单核苷酸多态性（SNP）是否是ABCB1过表达的机制。
采用序列特异性引物PCR（SSP-PCR）对101例胃癌多药耐药病例和100例对照进行基因分型。通过实时PCR对70例多药耐药病例和54例对照的基因表达进行评估。两组之间的相关性基于生物信息学工具预测的RNA二级结构。
基因分型结果显示，在研究的3个SNP中，rs28381943和rs2032586在患者组和对照组之间存在显著差异，但C3435T在两组之间没有差异。实时PCR结果显示，当我们将数据与平均模式下的每种基因型进行比较时，ABCB1表达上调。对存在2个相关SNP（rs28381943和rs2032586）时的二级结构预测表明，原始mRNA的ΔG值高于上述2个SNP的ΔG值。
我们观察到，我们研究的2个SNP（rs283821943和rs2032586）可能通过增加mRNA稳定性来提高ABCB1基因的表达，而C3435T并非如此。
