环磷酰胺体内干预对肾上腺皮质癌细胞ABCG2表达的影响

Cyclophosphamide intervention in vivo increases the ABCG2 expression in adrenocortical carcinoma cells

目的肿瘤高表达多药耐药相关转运蛋白三磷酸腺苷结合转运蛋白G家族成员2(ATP-binding cassette super family G member 2,ABCG2)是造成耐药及化疗失败的主要原因。文中旨在探讨环磷酰胺体内干预后肾上腺皮质癌细胞中ABCG2表达的意义。方法 BALB/C-nu裸鼠共10只,雌雄不拘,随机数表法分为对照组和环磷酰胺组,每组5只。将SW-13细胞注射入裸鼠皮下建立裸鼠皮下移植瘤模型,环磷酰胺组予腹腔注射环磷酰胺,对照组予注射等量等渗盐水,并对获得的2组瘤体组织进行原代培养。用免疫组化法(阳性肿瘤细胞百分比<10%者为阴性,≥10%为阳性)和流式细胞法分别检测瘤体组织及原代细胞株ABCG2的表达。结果流式细胞法检测ABCG2在环磷酰胺组细胞中表达率[(97.89±1.36)%]高于对照组细胞[(81.88±8.31)%],差异有统计学意义(P<0.05),免疫组化结果提示环磷酰胺组瘤体组织中ABCG2表达阳性率[(69.1±1.83)%]高于对照组[(53.4±1.65)%],差异有统计学意义(P<0.05)。结论多药耐药基因ABCG2参与肾上腺皮质癌耐药,可能为肾上腺皮质癌干预靶点。

Objective High expression of multi-resistant transporter ATP-binding cassette super family G member 2 （ABCG2） is a major cause of drug resistance and chemotherapeutic failure of cancer .This study was to investigate the significance of ABCG2 expression in adrenocortical cancer cells after cyclophosphamide （ CTX） intervention in vivo . Methods Ten male and fe-male BALB/C-nu mice were randomly divided into a cyclophosphamide （ CTX） group and a control of equal number .SW-13 cells were subcutaneously injected into the nude mice to establish a model of subcutaneous transplantation tumor , followed by intraperitoneal injec-tion of CTX and isotonic saline solution into the two groups of mice , respectively .Then the expression of ABCG 2 in tumor tissue and primarily cultured cells was detected by immunohistochemistry and flow cytometry . Results The expression of ABCG 2 in the tumor tissue was significantly higher in the CTX than in the control group （[69.1 ±1.83]%vs [53.4 ±1.65]%, P〈0.05）, and so was that in the primarily cultured cells （[97.89 ±1.36]% vs [81.88 ±8.31]%, P〈0.05）. Conclusion The ABCG2 gene is in-volved in the drug resistance of adrenocortical carcinoma and may be a therapeutic target of the malignancy .