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

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mRNA 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mRNA 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mRNA 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。

Abstract:

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.