索拉非尼联合三氧化二砷对肝癌表面耐药蛋白P-糖蛋白表达的影响及疗效观察

Effects of sorafenib combined with arsenic trioxide on the expression of surface drug resistance protein P-glycoprotein in patients with primary hepatocellular carcinoma and its clinical efficacy

目的探讨索拉非尼联合三氧化二砷治疗原发性肝癌的临床疗效,并研究其对肝癌组织耐药蛋白P-糖蛋白(P-GP)表达水平的影响。方法选取2017年1月至12月肿瘤内科收治的90例初次确诊原发性肝癌患者,按入院先后随机分成2组,观察组35例患者给予口服索拉非尼及注射三氧化二砷,对照组55例患者给予注射三氧化二砷。采用免疫组织化学染色法检测2组患者治疗前后肝癌组织及配对癌周组织中P-GP表达水平,并观察2组近期疗效、远期疗效及不良反应发生情况。结果原发性肝癌晚期患者癌组织、癌旁组织及正常组织中P-GP表达的阳性率分别为69.09%、32.73%、16.36%;2组均治疗4个疗程后,观察组患者癌组织及癌旁组织P-GP表达阳性率较治疗前明显降低(P<0.05),而2组正常组织中P-gp表达阳性率前后差异无统计学意义(P>0.05),观察组患者癌组织及癌旁组织中P-GP表达阳性率均明显低于对照组,差异有统计学意义(P>0.05);观察组总有效率及疾病控制率、中位TTP及12个月生存率明显高于对照组,差异均有统计学意义(P<0.05);2组不良反应发生率差异无统计学意义(P>0.05)。结论索拉非尼联合三氧化二砷可明显提升原发性肝癌临床治疗效果,可能与下调癌组织及癌旁组织中P-GP的表达有关。

Objective To investigate the clinical efficacy of sorafenib combined with arsenic trioxide in treatment of primary liver cancer,and to explore its effects on the expression of P-glycoprotein(P-GP).Methods A total of 90 patients with primary liver cancer who were diagnosed for the first time and treated in department of oncology of our hospital from January to December 2017 were enrolled in the study.According to the admission time,these patients were randomly divided into two groups.The 35 patients in observation group were treated by oral sorafenib and arsenic trioxide injection,however,the 55 patients in control group were treated by arsenic trioxide injection only.Immunohistochemical staining was used to detect the expression levels of P-GP in liver cancer tissues and corresponding para-cancerous tissues before and after treatment.Moreover the short-term efficacy,long-term efficacy and adverse reactions were observed and compared between the two groups.Results The positive rates of P-GP in cancer tissues,paracancerous tissues and normal tissues of patients with advanced liver cancer were 69.09%,32.73%and 16.36%,respectively.After 4 treatment courses,the positive expressioon rate of P-GP in cancer tissues and adjacent tissues in observation group was significantly lower than that before treatment(P<0.05),however,there was no significant difference in the positive expression rate of P-GP in normal tissues of both groups before and after treatment(P>0.05).Moreover positive expression rate of P-GP in cancer tissues and adjacent tissues in observation group was significantly lower than that in control group(P>0.05).The total effective rate and disease control rate,median TTP and 12-month survival rate in observation group were significantly higher than those in control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Sorafenib combined with arsenic trioxide can significantly improve the clinical therapeutic effects on primary liver cancer,which may be related with the down-regulation of P-GP expression in cancer tissues and adjacent tissues.