胃癌组织核转录因子κB p65蛋白表达与肿瘤多药耐药性的关系

Relationship Between the Protein Expression of Nuclear Transcription Factors κB p65 and Multidrug Resistance in Gastric Cancer

目的分析胃癌组织中核转录因子κB(NF-κB)p65蛋白表达与肿瘤多药耐药性(MDR)的关系,并探讨其意义。方法选取2013年1—12月在河北医科大学第四医院外三科手术切除并经病理证实的68例胃癌患者的肿瘤组织及癌旁组织。采用免疫组化(SP)法检测胃癌组织及癌旁组织NF-κB p65、P-gp、Bcl-2、Bax蛋白表达;采用体外药物敏感实验(MTT法)检测胃癌组织细胞对氟尿嘧啶(5-FU)、长春新碱(VCR)、紫杉醇(PTX)、奥沙利铂(L-OHP)、表阿霉素(e ADM)的体外化疗药物敏感性。结果胃癌组织NF-κB p65、P-gp、Bcl-2蛋白强表达率均高于癌旁组织,Bax蛋白强表达率低于癌旁组织,差异均有统计学意义(P<0.05)。Spearman相关分析结果显示,胃癌组织NF-κB p65与P-gp蛋白表达呈正相关(rs=0.321,P=0.008),NF-κB p65与Bax蛋白表达呈负相关(rs=-0.333,P=0.006),NF-κB p65与Bcl-2蛋白表达无直线相关关系(rs=0.231,P=0.058)。在胃癌组织中,5-FU、PTX对NF-κB p65强表达者肿瘤细胞抑制率低于弱表达者,差异有统计学意义(P<0.05);5-FU、PTX、L-OHP对P-gp强表达者肿瘤细胞抑制率低于弱表达者,差异有统计学意义(P<0.05);5-FU、PTX、e ADM对Bcl-2强表达者肿瘤细胞抑制率低于弱表达者,差异有统计学意义(P<0.05);5-FU、L-OHP、e ADM对Bax强表达者肿瘤细胞抑制率高于弱表达者,差异有统计学意义(P<0.05)。结论胃癌组织中NF-κB p65表达增高,其可能通过调控P-gp、Bax蛋白表达而参与胃癌MDR。

Objective To investigate the relationship between the protein expression of gastric cancer tissue nuclear transcription factors κB （NF-KB） p65 and the multidrug resistance （MDR） of tumor and explore its significance. Methods We Collected the tumor tissue and para - carcinoma tissue of 68 patients who were pathologically diagnosed with gastric carcinoma and underwent excision surgery in the Third Department of General Surgery of the Fourth Affiliated Hospital, Hebei Medical University from January 2013 to December 2013. Using immunohistochemical SP method, the protein expression levels of NF-κB p65, P-gp, Bcl-2 and Bax in the collected tissues were detected. Using MTT method, the sensitivity of gastric cancer cells towards 5-FU, VCR, PTX, L-OHP and eADM was measured. Results The strong expression incidence of NF-κB p65, P-gp, Bcl-2 proteins in cancer tissues was higher than that in para - carcinoma tissues, while Bax protein in cancer tissues was lower than that in para - cancer tissues （ P 〈 0.05 ）. Spearman correlation analysis showed that positive relationship was found between the expression levels of NF-κB p65 and P-gp （ rs= 0. 321, P = 0. 008 ） ; expression of NF-KB p65 and that of Bax had negative correlation （ rs = - 0. 333, P = 0. 006）, and the expression of NF-κB p65 had no significant correlation with that of Bcl-2 （ rs = 0. 231, P =0. 058）. In .gastric cancer tissues with strong expression of NF-KB p65, the inhibition rates of 5-FU and PTX for cancer ceils were lower than those tissues with weak expression of NF-κB p65 （ P 〈 0.05 ） ; in tissues with strong expression of P-gp, the inhibition rates of 5-FU, PTX and L-OHP for cancer cells were lower than tissues with weak expression of P-gp （ P 〈 0. 05 ） ; inhibition rates of 5-FU, PTX, eADM to cancer cells were lower in tissues with strong expression of Bcl-2 than tissues with weak expression of Bcl-2 （P 〈0. 05） , whereas in tissues with strong, expression of Bax, inhibition rates of5-FU, L-OHP and eADM to cancer cells were higher than tissues with weak expression of Bax （ P 〈 0. 05 ）. Conclusion Gastric cancer tissues have higher expression of NF-κB p65 which might be involved in MDR of gastric cancer by regulating P-gp and Bax proteins.