OCTN2与前列腺癌细胞对奥沙利铂化疗敏感性的相关性
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篇名: OCTN2与前列腺癌细胞对奥沙利铂化疗敏感性的相关性
TITLE: Correlation of OCTN2 with the chemosensitivity of prostate cancer cells to oxaliplatin
摘要: 目的 研究新型有机阳离子转运体2(OCTN2)与前列腺癌细胞对奥沙利铂化疗敏感性的相关性。方法收集行前列腺癌根治术患者的前列腺癌组织标本,采用免疫组化法检查组织中的OCTN2蛋白表达;培养标本原代细胞得到前列腺癌细胞株。采用电感耦合等离子体质谱法检测癌细胞对低浓度(0.1μmol/L)奥沙利铂的摄取量,采用RealtimePCR及Westernblot法检测癌细胞中OCTN2mRNA及蛋白的表达水平;选择OCTN2蛋白表达最高及最低的前列腺癌细胞株,采用三磷酸腺苷肿瘤药物敏感性检测法(ATP-TCA)计算奥沙利铂对癌细胞的半数抑制浓度(IC50);采用MTT法检测血药峰浓度奥沙利铂(50μmol/L)对前列腺癌细胞的抑制率。采用Spearman法分析前列腺癌细胞对奥沙利铂摄取量与奥沙利铂对前列腺癌细胞抑制率及OCTN2mRNA表达的相关性。结果OCTN2定位于癌细胞膜;癌细胞对奥沙利铂的摄取量为0.283±0.264(n=12);不同癌细胞中OCTN2mRNA和蛋白表达差异明显;OCTN2高表达的癌细胞对奥沙利铂的敏感性(IC50为4.61μmol/L)高于OCTN2低表达的癌细胞(IC50为26.23μmol/L)。奥沙利铂对癌细胞的抑制率为(25.4±10.8)%(n=12)。前列腺癌细胞对奥沙利铂的摄取量与奥沙利铂对前列腺癌细胞的增殖抑制率及前列腺癌细胞中OCTN2mRNA表达水平三者间存在相关性(P<0.05)。结论OCTN2高表达可能促进前列腺癌细胞对奥沙利铂的摄取,其表达水平可作为预测前列腺癌细胞对奥沙利铂化疗敏感性的参考依据之一。
ABSTRACT: OBJECTIVE To study the correlation of novel organic cation transporter 2 (OCTN2) with the chemosensitivity of prostate cancer cells to oxaliplatin. METHODS Tumor samples of patients receiving radical prostatectomy were collected, and OCTN2 protein was detected with immunohistochemistry; the primary cells of the specimen were cultivated to obtain prostate cancer cell line. Inductively coupled plasma mass spectrometry was used to detect the uptake of low concentration (0.1 μmol/L) of oxaliplatin by cancer cells. Real-time PCR and Western blot were used to detect the mRNA and protein expressions of OCTN2 in cancer cells; the prostate cancer cells with the highest and lowest expression of OCTN2 protein were selected, and IC50 of oxaliplatin to prostate cancer cells was analyzed by ATP-TCA method. The inhibitory rate of plasma peak concentration of oxaliplatin (50 μmol/L) to prostate cancer cells was detected by MTT assay. Spearman method was used to analyze the relationship of the uptake of oxaliplatin by prostate cancer cells with inhibitory rate of oxaliplatin to prostate cancer cells and 505916443@qq.com mRNA expressions of OCTN2. RESULTS OCTN2 was located on the membrane of cancer cells, and the uptake of zjdtztougao@163.com oxaliplatin by cancer cells was 0.283±0.264 (n=12)mRNA and protein expression of OCTN2 varied significantly among different cancer cells. The sensitivity of cancer cells with high expression of OCTN2 to oxaliplatin (IC50 of 4.61 μmol/L) was higher than that of cancer cells with lower expression of OCTN2 (IC50 of 26.23 μmol/L). The inhibitory rate of oxaliplatin to cancer cells was (25.4±10.8)% (n=12). There was a correlation between the uptake of oxaliplatin by prostate cancer cells and the inhibition rate of oxaliplatin to prostate cancer cells and mRNA expression of OCTN2 (P<0.05). CONCLUSIONS High-expressed OCTN2 may promote the uptake of oxaliplatin by prostate cancer cells, and its expression can serve as a reference for predicting the sensitivity of prostate cancer cells to oxaliplatin chemotherapy.
期刊: 2023年第34卷第12期
作者: 褚雷;徐斌;沙德厚;王磊;程广舟;张继东
AUTHORS: CHU Lei,XU Bin,SHA Dehou,WANG Lei,CHENG Guangzhou,ZHANG Jidong
关键字: 新型有机阳离子转运体2;奥沙利铂;前列腺癌细胞;化疗敏感性
KEYWORDS: novel organic cation transporter 2; oxaliplatin; prostate cancer cell; chemosensitivity
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