他莫昔芬增强了传统化疗对食管腺癌细胞的细胞毒性。

Tamoxifen enhances the cytotoxicity of conventional chemotherapy in esophageal adenocarcinoma cells.

作者信息

Due S L, Watson D I, Bastian I, Ding G Q, Sukocheva O A, Astill D St J, Vat L, Hussey D J

机构信息

Flinders University Department of Surgery and Flinders Centre for Cancer Prevention and Control, Flinders Medical Centre, Adelaide, South Australia, Australia.

Department of Anatomical Pathology, Flinders Medical Centre, Adelaide, South Australia, Australia.

出版信息

Surg Oncol. 2016 Sep;25(3):269-77. doi: 10.1016/j.suronc.2016.05.029. Epub 2016 May 27.

DOI:10.1016/j.suronc.2016.05.029

PMID:27566033

Abstract

INTRODUCTION

Esophageal adenocarcinoma is a lethal malignancy which is increasing in incidence, and many patients receive chemotherapy as part of their treatment. We have previously demonstrated that esophageal adenocarcinoma-derived cell lines respond to treatment with estrogen receptor modulators, such as tamoxifen. Reports from breast cancer suggest that tamoxifen may attenuate the efficacy of other chemotherapeutic agents. We have therefore assessed the response of esophageal adenocarcinoma cell lines to tamoxifen therapy when given in combination with conventional agents.

METHODS

Two estrogen receptor (ER)-positive esophageal adenocarcinoma cell lines (OE-19 and OE-33) were treated with combinations of tamoxifen, cisplatin and 5-fluorouracil (5-FU). Effects on cell viability were measured using an MTS assay, and cell death was detected with annexin V/propidium iodide flow cytometry. To assess whether the efficacy of tamoxifen in these cell lines might be relevant to the clinical setting, we analyzed ER status in 10 esophageal adenocarcinoma tissue specimens by immunohistochemistry.

RESULTS

IC50 values (μM) for OE-19 and OE-33 were 11.2 and 7.1 for tamoxifen, 19.6 and 4.7 for cisplatin, and 1.7 and 5.9 for 5-FU, respectively. Cell death was detected in 11.9% and 15.8% of cells treated with tamoxifen, 7.9% and 8.7% cells treated with cisplatin, and 3.6% and 8.6% cells treated with 5-FU at their IC50s. The addition of tamoxifen to cisplatin increased cell death by 11.4% in OE-19 (p < 0.0001) and 16.3% in OE-33 (p < 0.0001). Similarly, the addition of tamoxifen to 5-FU increased cell death by 11.6% in OE-19 (p < 0.0001) and 15.9% in OE-33 (p < 0.0001). Eight of 10 tissue specimens showed positive staining for ERα and 7 of 10 for ERβ.

CONCLUSIONS

In a cell culture model the addition of tamoxifen to conventional chemotherapy appears to be both feasible and beneficial. Expression of ERα and ERβ was also confirmed in esophageal adenocarcinoma tissues.

摘要

引言

食管腺癌是一种致命的恶性肿瘤，其发病率正在上升，许多患者接受化疗作为治疗的一部分。我们之前已经证明，食管腺癌来源的细胞系对雌激素受体调节剂（如他莫昔芬）治疗有反应。乳腺癌的报告表明，他莫昔芬可能会减弱其他化疗药物的疗效。因此，我们评估了食管腺癌细胞系在与传统药物联合使用时对他莫昔芬治疗的反应。

方法

用他莫昔芬、顺铂和5-氟尿嘧啶（5-FU）的组合处理两种雌激素受体（ER）阳性的食管腺癌细胞系（OE-19和OE-33）。使用MTS测定法测量对细胞活力的影响，并用膜联蛋白V/碘化丙啶流式细胞术检测细胞死亡。为了评估他莫昔芬在这些细胞系中的疗效是否可能与临床情况相关，我们通过免疫组织化学分析了10例食管腺癌组织标本中的ER状态。

结果

OE-19和OE-33的半数抑制浓度（IC50）值（μM）分别为：他莫昔芬为11.2和7.1，顺铂为19.6和4.7，5-FU为1.7和5.9。在IC50浓度下，用他莫昔芬处理的细胞中分别有11.9%和15.8%发生细胞死亡，用顺铂处理的细胞中有7.9%和8.7%，用5-FU处理的细胞中有3.6%和8.6%。在顺铂中加入他莫昔芬使OE-19中的细胞死亡增加了11.4%（p<0.0001），在OE-33中增加了16.3%（p<0.0001）。同样，在5-FU中加入他莫昔芬使OE-19中的细胞死亡增加了11.6%（p<0.0001），在OE-33中增加了15.9%（p<0.0001）。10个组织标本中有8个显示ERα染色阳性，10个中有7个显示ERβ染色阳性。