塞来昔布联合FOLFOX4方案治疗晚期胃癌的疗效及机制研究  

Therapeutic effect of Celecoxib combined with FOLFOX4 on advanced gastric cancer

作　　者：任晓晓 张小茜[2] 张红梅[2] 冯玉光[2] 董秀红[2] 史立宏[3] 邵翠 Xiao-xiao Ren;Xiao-qian Zhang;Hong-mei Zhang;Yu-guang Feng;Xiu-hong Dong;Li-hong Shi;Cui Shao(Graduate school of Weifang Medical College, Weifang, Shandong 261053, China;Department of Gastroenterology, Afliated Hospital of Weifang Medical College, Weifang, Shandong 261031, China;Department of Pharmacology, Weifang Medical College, Weifang, Shandong 261053, China)

机构地区：[1]潍坊医学院研究生院,山东潍坊261053 [2]潍坊医学院附属医院消化内科,山东潍坊261031 [3]潍坊医学院药理学教研室,山东潍坊261053

出　　处：《中国现代医学杂志》2018年第15期27-31,共5页China Journal of Modern Medicine

基　　金：山东省自然科学基金(No:ZR2015HL016);本成果得到潍坊医学院公派教师出国访学项目经费资助

摘　　要：目的探讨塞来昔布联合FOLFOX4方案治疗人晚期胃癌的效果及可能的作用机制。方法选取2015年9月-2017年5月潍坊医学院附属医院消化科就诊的符合条件的经电子胃镜和病理证实为晚期胃癌的患者,共80例。随机分成两组,其中实验组40例,应用塞来昔布联合FOLFOX4化疗方案,对照组40例,应用FOLFOX4化疗方案。根据治疗效果的不同分为完全缓解(CR)、部分缓解(PR)、稳定(SD)和进展(PD)。参考WHO实体瘤疗效评价标准评价治疗效果。分别采用逆转录聚合酶链反应(RT-PCR)、免疫组织化学、Western blot检测治疗后胃癌组织中ABCG2、OCT-4、HIF-2α的m RNA及其蛋白表达。结果80例患者经过4周期治疗后,实验组有效率为77.5%,对照组有效率为42.5%,差异有统计学意义(P<0.05),实验组与对照组HIF-2α、ABCG2、OCT-4的m RNA和蛋白相对表达量差异均有统计学意义(P<0.05)。实验组表达减弱。结论塞来昔布联合FOLFOX4治疗晚期胃癌有效率高于FOLFOX4方案,胃癌组织中ABCG2、OCT-4、HIF-2α的m RNA和蛋白表达量降低,其机制可能通过降低HIF-2α-ABCG2和HIF-2α-OCT-4通路的表达影响胃癌的发展和转移,进而影响肿瘤的化疗抵抗、多药耐药。Objective To assess the therapeutic effects of celecoxib combined with FOLFOX4 chemotherapy on human advanced gastric cancer and the possible mechanisms. Methods A total of 80 patients diagnosed with advanced gastric cancer were admitted to our hospital from September 2015 to May 2017. Patients in control group received standard treatment of FOLFOX4, and 40 cases in observation group were treated with additional Celecoxib. Efficacy of treatments were recorded as complete remission（CR）, partial remission（PR）, stable disease（SD） and progressive disease（PD）. The expressions of ABCG2, OCT-4, HIF-2α in gastric cancer tissues were detected by RTPCR, immunohistochemical or Western blot. Results Effective rate in observation group was significantly higher when compared with that in control group（77.5% vs 42.5%, P〈0.05）. Expression of HIF-2α, ABCG2, OCT-4 in observation group was dramatically decreased compared with control group（P〈0.05）. Conclusions Celecoxib combined with FOLFOX4 is a promising treatment for the treatment of advanced gastric cancer, which exerts therapeutic effect through inhibiting HIF-2α-ABCG2 and HIF-2α-Oct-4 signaling pathway.

关 键 词：胃癌 塞来昔布 多药耐药 

分 类 号：R735.2[医药卫生—肿瘤]