毒结清口服液对中晚期肿瘤化疗患者MGMT基因甲基化的影响

目的观察毒结清口服液对中晚期肿瘤化疗患者血浆中O6-甲基鸟嘌呤-DNA-甲基转移酶(O6-methylguanine-DNA methyltransferase,MGMT)基因甲基化状态的影响。方法收集中晚期肿瘤化疗患者60例,随机分为治疗组(30例,常规化疗+毒结清口服液20mL/次,每日3次)和对照组(30例,单用化疗),疗程8周,治疗前后用巢式甲基化特异性聚合酶链反应(MSP)检测中晚期肿瘤化疗患者血浆中MGMT基因的甲基化状态,同时检测外周血常规、KPS评分,评估临床疗效及毒副反应。结果 MGMT基因甲基化检测结果显示治疗组、对照组甲基化率分别为20.00%、46.67%,差异有统计学意义(P<0.05)。与治疗前比较,治疗后治疗组KPS评分显著提高,对照组显著下降,差异均有统计学意义(P<0.05)。两组治疗后比较,差异亦有统计学意义(P<0.01)。化疗后治疗组毒副反应较对照组轻(P<0.01)。结论毒结清口服液对化疗有增效减毒作用,且不影响骨髓造血功能。其作用靶点可能是MGMT,通过对MGMT活性的调控达到增效减毒的作用。

Effects of Dujieqing Oral Uquid on the Promoter Methylation of the MQMT Gene in Middle-and-late Stage Tumor Patients ReceMng Chemotherapy

Objective To observe the effects of Dujieqing Oral Liquid （DJQ） on the promoter methylation of the O^6-methylguanine-DNA methyltransferase （MGMT） gene in the plasma DNA samples from middle-and-late stage tumor patients receiving chemotherapy. Methods Recruited 60 patients were randomly assigned to the treatment group （treated by conventional chemotherapy combined DJQ, 20 mL each time, three times daily） and the control group （treated by chemotherapy alone）, 30 in each group. The therapeutic course was 8 weeks. The promoter methylation of the MGMT gene in the plasma DNA samples form middle-and-late stage tumor patients receiving chemotherapy was detected before and after treatment using nested methylation-specific polymerase chain reaction （MSP）. Meanwhile, the peripheral hemogram was detected. The clinical efficacy and toxic/ad- verse reactions were assessed using Karnofsky performance scale （KPS）. Results Results of the promoter methylation of MGMT genes showed that methylation rate was 20.00% in the treatment group and 46. 67% in the control group （P 〈0.05）. Compared with before treatment, the KPS was significantly improved in the treatment group after treatment, while it significantly decreased in the control group after treatment （both P 〈0.05） . There was statistical difference in the KPS between the two groups after treatment （P 〈0.01 ）. The toxic/adverse reac- tions were milder in the treatment group than in the control group （ P 〈0.01 ）. Conclusions DJQ showed efficien- cy synergism and toxicity reducing effects, but with no effect on the hematopoietic function of the bone marrow. MGMT gene was indicated as DJQ＇s target point for efficiency synergism and toxicity reducing. The efficiency synergism and toxicity reducing effects were achieved by regulating the activities of MGMT gene.