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曲妥珠单抗联合化疗药物治疗胃癌细胞系中 HER-2/neu（erbB-2）表达水平与疗效的相关性。

Correlation between HER-2/neu(erbB-2) expression level and therapeutic effect of combination treatment with HERCEPTIN and chemotherapeutic agents in gastric cancer cell lines.

机构信息

Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.

Jilin Cancer Hospital, Changchun, China.

出版信息

Cancer Cell Int. 2014 Jan 29;14(1):10. doi: 10.1186/1475-2867-14-10.

DOI:10.1186/1475-2867-14-10
PMID:24472145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3915235/
Abstract

INTRODUCTION

Although advanced gastric cancer has many limitations and response rate is marginal in chemotherapy. Overexpression of human epidermal growth factor receptor 2(HER-2/neu) gene and its protein are associated with increased cell division and a high rate of tumor growth and have been reported in several malignancies. Especially, approximately 30% of breast cancer patients have overexpression of HER-2/neu protein and the overexpression metastasize faster, induces resistance of the chemotherapy and down-regulate function of estrogen receptor. Recombinant humanized anti-HER2 antibody (Herceptin) inhibits proliferation of HER-2/neu overexpressing tumor cells and the use of that in combination in metastatic breast cancer have increased cytotoxicity of chemotherapeutic agents.

METHODS

We evaluated the expression of HER-2/neu protein in gastric cell lines by FACS and then comparing the cytotoxicity in chemotherapeutics (doxorubicin, cisplatin, paclitaxel, 5-FU) alone and in combination with Herceptin according to the expression of HER-2/neu protein by MTT assay.

RESULTS

  1. NCI-N87 (88%) gastric cancer cell line and SK-BR-3 (89%) breast cancer cell line with strong positivity of HER-2/neu expression. YBC-2 (55%) and YBC-3 (48%) gastric cancer cell line with intermediated, weak positivity respectively. Negative control U-87 MG (6%) brain cancer cell line were showed low expression of HER-2/neu. 2. Cell growth was dose-dependently inhibited in HER-2/neu positive, control cell line SK-BR-3 by Herceptin treatment but not observed in HER-2/neu negative control cell line U-87 MG. Effective growth inhibition was not observed in gastric cancer cell lines with single treatment of Herceptin, all cell lines observed the dose-dependent growth inhibition to chemotherapeutic agents (doxorubicin, cisplatin, paclitaxel and 5-FU). 3. Combination of Herceptin with doxorubicin observed synergistic effects in all cancer cell lines except YBC-3, combination of Herceptin with cisplatin observed NCI-N87 and SK-BR-3 and combination of Herceptin with paclitaxel observed synergistic effects in YBC-2. Combination of Herceptin with 5-FU observed antagonistic effects in all cancer cell lines.

CONCLUSIONS

According to HER-2/neu expression level, effect of anti-cancer agents was observed differently in combination of Herceptin with chemotherapeutic agents. This suggests that HER-2/neu expression level can be applied standard of combination drug selection in combination of Herceptin With chemotherapeutic agents in gastric cancer.

摘要

简介

尽管晚期胃癌的化疗效果有限，反应率也较低，但人表皮生长因子受体 2（HER-2/neu）基因及其蛋白的过度表达与细胞分裂增加和肿瘤生长速度加快有关，已在多种恶性肿瘤中报道。特别是，约 30%的乳腺癌患者存在 HER-2/neu 蛋白过度表达，过度表达会导致肿瘤更快转移，诱导化疗耐药，并下调雌激素受体功能。重组人源化抗 HER2 抗体（赫赛汀）可抑制 HER-2/neu 过度表达肿瘤细胞的增殖，将其与转移性乳腺癌联合应用可提高化疗药物的细胞毒性。

方法

我们通过流式细胞术评估了 HER-2/neu 蛋白在胃细胞系中的表达，然后通过 MTT 测定根据 HER-2/neu 蛋白的表达比较了单独使用和联合使用赫赛汀时化疗药物（阿霉素、顺铂、紫杉醇、5-FU）的细胞毒性。

结果

  1. NCI-N87（88%）胃癌细胞系和 SK-BR-3（89%）乳腺癌细胞系 HER-2/neu 表达呈强阳性。YBC-2（55%）和 YBC-3（48%）胃癌细胞系呈中等强度阳性。阴性对照 U-87 MG（6%）脑癌细胞系 HER-2/neu 表达较低。2. HER-2/neu 阳性对照细胞系 SK-BR-3 中，赫赛汀治疗呈剂量依赖性抑制细胞生长，但在 HER-2/neu 阴性对照细胞系 U-87 MG 中未见观察到。赫赛汀单药治疗对胃癌细胞系未见有效生长抑制，所有细胞系均观察到对化疗药物（阿霉素、顺铂、紫杉醇和 5-FU）的剂量依赖性生长抑制。3. 除 YBC-3 外，赫赛汀与阿霉素联合应用观察到协同作用，赫赛汀与顺铂联合应用观察到 NCI-N87 和 SK-BR-3 及赫赛汀与紫杉醇联合应用观察到协同作用。赫赛汀与 5-FU 联合应用在所有癌细胞系中观察到拮抗作用。

结论

根据 HER-2/neu 表达水平，赫赛汀联合化疗药物的抗癌效果不同。这表明 HER-2/neu 表达水平可作为胃癌中赫赛汀联合化疗药物选择的标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/3915235/160dbeb7bf23/1475-2867-14-10-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/3915235/0674e6b4fb07/1475-2867-14-10-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/3915235/056e65785e68/1475-2867-14-10-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/3915235/160dbeb7bf23/1475-2867-14-10-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/3915235/0674e6b4fb07/1475-2867-14-10-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/3915235/056e65785e68/1475-2867-14-10-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aaa/3915235/160dbeb7bf23/1475-2867-14-10-3.jpg

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