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Inhibitory effects of combinations of trastuzumab and cytotoxic chemotherapy drugs in HER2-positive gastric cancer
Frontiers in Life Science ( IF 1.333 ) Pub Date : 2021-03-29 , DOI: 10.1080/26895293.2021.1906330
Shu Zheng 1 , Guo-Bin Fu 1 , Hong-Chang Shen 1 , Qi Liu 1 , Wei-Bo Wang 1
Affiliation  

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a certain proportion of gastric cancer cases. Trastuzumab is a humanized monoclonal antibody that targets the HER2 receptor. Previous studies have demonstrated a synergistic interaction between trastuzumab and 5-fluorouracil/cisplatin in HER2-positive gastric cancer cells. However, it is unclear whether it is rational to combine trastuzumab with other chemotherapy regimens in clinical practice. We evaluated the growth inhibitory effects of combinations of trastuzumab and cytotoxic chemotherapy drugs in HER2-positive gastric cancer cell lines. HER2 protein expression was evaluated by Western blotting in five gastric cancer cell lines. MTT assays were performed to evaluate the growth inhibitory effects of trastuzumab and four chemotherapeutic agents, epirubicin, cisplatin, 5-fluorouracil and docetaxel, both alone and in combination. To explore the molecular mechanisms underlying the synergistic interactions of trastuzumab and chemotherapeutic agent treatment, the protein levels of phospho-protein kinase B (pAkt) were determined by Western blotting. We showed that trastuzumab synergizes with the cytotoxic effect of epirubicin in HER2-positive gastric cancer cells. Further investigation showed that the trastuzumab-epirubicin combination decreased the expression of pAkt. Altogether, our results provide preclinical evidence for the optimization of this combination regimen in the treatment of HER2-positive gastric cancer patients.



中文翻译:

曲妥珠单抗联合细胞毒性化疗药物对HER2阳性胃癌的抑制作用

人表皮生长因子受体2(HER2)蛋白在一定比例的胃癌病例中过表达。曲妥珠单抗是靶向HER2受体的人源化单克隆抗体。先前的研究表明曲妥珠单抗和5-氟尿嘧啶/顺铂在HER2阳性胃癌细胞中具有协同作用。然而,目前尚不清楚在临床实践中将曲妥珠单抗与其他化疗方案联合使用是否合理。我们评估了曲妥珠单抗和细胞毒性化学治疗药物组合在HER2阳性胃癌细胞系中的生长抑制作用。通过蛋白质印迹法评估了5种胃癌细胞系中的HER2蛋白表达。进行MTT分析以评估曲妥珠单抗和四种化学治疗剂表柔比星,顺铂,5-氟尿嘧啶和多西他赛,单独或组合使用。为了探索潜在的曲妥珠单抗和化学治疗剂协同相互作用的分子机制,通过蛋白质印迹法测定磷酸化蛋白激酶B(pAkt)的蛋白水平。我们显示曲妥珠单抗与表柔比星在HER2阳性胃癌细胞中的细胞毒性作用协同作用。进一步的研究表明曲妥珠单抗-表柔比星联合降低了pAkt的表达。总之,我们的结果为优化这种联合治疗HER2阳性胃癌患者的治疗提供了临床前证据。通过蛋白质印迹法测定磷酸化蛋白激酶B(pAkt)的蛋白水平。我们显示曲妥珠单抗与表柔比星在HER2阳性胃癌细胞中的细胞毒性作用协同作用。进一步的研究表明曲妥珠单抗-表柔比星联合降低了pAkt的表达。总之,我们的结果为优化这种联合治疗HER2阳性胃癌患者的治疗提供了临床前证据。通过蛋白质印迹法测定磷酸化蛋白激酶B(pAkt)的蛋白水平。我们显示曲妥珠单抗与表柔比星在HER2阳性胃癌细胞中的细胞毒性作用协同作用。进一步的研究表明曲妥珠单抗-表柔比星联合降低了pAkt的表达。总之,我们的结果为优化这种联合治疗HER2阳性胃癌患者的治疗提供了临床前证据。

更新日期:2021-03-29
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