非小细胞肺癌组织中ABCG4表达与耐药的相关性研究

The correlation of ABCG4 expression with drug resistance in non-small cell lung cancer

目的检测ABCG4 mRNA和蛋白在非小细胞肺癌(NSCLC)组织中的表达,分析其表达与病理类型及NSCLC细胞耐药的相关性,为研究其耐药机制提供理论基础。方法采用免疫组化染色、RT-PCR及Western blotting检测ABCG4在NSCLC组织中的表达;MTT法检测NSCLC对化疗药物的敏感性,分析药物敏感性与ABCG4 mRNA和蛋白表达的相关性。结果 ABCG4蛋白阳性主要定位于细胞膜和胞质,其在NSCLC组织中的阳性表达率为73.9%(68/92),而在30例癌旁正常肺组织中几乎不表达。ABCG4蛋白在肺鳞癌和肺腺癌中的阳性表达率分别为67.3%和81.4%,差异无统计学意义(P>0.05)。环磷酰胺、吉西他滨、多柔比星、紫杉醇和顺铂在NSCLC组织中的药物敏感程度与其相应组织中ABCG4蛋白阳性表达有关(rs均>0.3,P均<0.05);除紫杉醇外,环磷酰胺、吉西他滨、多柔比星和顺铂在NSCLC组织中的药物敏感程度与其相应组织中ABCG4 mRNA表达量有关(P均<0.05)。结论 ABCG4在肺鳞癌、肺腺癌中高表达,其表达程度与NSCLC部分化疗药物耐药有关,为进一步研究ABCG4在NSCLC中的表达及可能耐药机制提供实验依据。

Objective To detect the expression of ABCG4 mRNA and protein in non-small cell lung cancer （NSCLC）, and to analyze the relationship between the expression and pathological types, drug resistance of NSCLC cells. Methods Immunohistochemical staining, RT-PCR and Western blotting were used to detect the expression of ABCG4 mRNA and protein in NSCLC tissues. MTT assay was used to detect the sensitivity of NSCLC cells to chemotherapeutic drugs, and the relationship between drug sensitivity and the expression of ABCG4 mRNA and protein was analyzed. Results The positive expression of ABCG4 protein was mainly located in the cell membrane and cytoplasm. The positive expression rate of ABCG protein in NSCLC was 73.9（68/92） , but was not expressed in 30 cases of adjacent non tumorous lung tissues. The positive expression rate of ABCG4 protein in lung squamous cell carcinoma and lung adenocarcinoma was 67. 3% and 81.4% without statistical diference （P〉0. 05）. The drug sensitivity of cyclophosphamide, gemcit- abine, doxorubicin, paclitaxel and eisplatin in NSCLC tissues was related to the positive expression of ABCG4 protein in the corre- sponding tissues （rs 〉0. 3, P〈0. 05）. Except for paclitaxel, drug sensitivity of cyclophosphamide, gemcitabine, doxorubicin and cispla- tin in NSCLC tissues was related to the expression of ABCG4 mRNA in the corresponding tissues （P〈0.05）. Conclusion The AB- CG4 mRNA and protein are overexpressed in squamous cell lung cancer and adenocarcinoma. The expression of ABCG4 mRNA and protein may be related to chemoresistance in NSCLC, which provides experimental basis for further study on ABCG4 chemoresistance and its mechanism in NSCLC.