S100P 增强人胃癌细胞系的化疗敏感性。

S100P enhances the chemosensitivity of human gastric cancer cell lines.

机构信息

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

出版信息

Cancer Biomark. 2013;13(1):1-10. doi: 10.3233/CBM-130330.

DOI:10.3233/CBM-130330

PMID:23736016

Abstract

BACKGROUND

The effect of the protein S100P on biological characteristics of cancer is not clear, especially in gastric cancer. We previously showed that S100P positive gastric cancer patients have a better cumulative survival than S100P negative patients.

OBJECTIVE

To study the possible mechanisms of S100P enhanced the chemosensitivity to oxaliplatin in gastric cancer cell lines.

METHODS

S100P was overexpressed in vitro by plasmid transfection and downregulated by siRNA transfection in the BGC823 and SGC7901 gastric cancer cell lines. Cell survival rate, changes in the chemoresistance gene, such as GST-π, MDR1, MRP1, Topo-II, MVP and BCRP, intake of anticancer drug were measured after oxaliplatin treatment.

RESULTS

In SGC7901 cells, MTT assay indicated that increased S100P expression levels decreased the survival rate and decreased S100P expression levels increased the survival rate. In BGC823 and SGC7901 cell lines, mRNA of MDR1, a chemoresistance genes, was decreased in cells that overexpressed S100P, and increased in cells with downregulation of S100P. Intracellular accumulation of platinum increased in cells with overexpressed S100P, and decreased in cells with S100P downregulation.

CONCLUSIONS

S100P contributes to oxaliplatin chemosensitivity in gastric cell lines by increasing drug inflow. It might also be a novel independent prognostic factor in gastric cancer patients who receive adjuvant chemotherapy with oxaliplatin.

摘要

背景

蛋白 S100P 对癌症生物学特性的影响尚不清楚，特别是在胃癌中。我们之前的研究表明，S100P 阳性的胃癌患者的累积生存率优于 S100P 阴性患者。

目的

研究 S100P 增强胃癌细胞系对奥沙利铂化疗敏感性的可能机制。

方法

通过质粒转染在 BGC823 和 SGC7901 胃癌细胞系中过表达 S100P，通过 siRNA 转染下调 S100P 的表达。奥沙利铂处理后，检测细胞存活率、化疗耐药基因 GST-π、MDR1、MRP1、Topo-II、MVP 和 BCRP 的变化以及抗癌药物的摄取。

结果

在 SGC7901 细胞中，MTT 检测表明，S100P 表达水平的增加降低了细胞存活率，而 S100P 表达水平的降低增加了细胞存活率。在 BGC823 和 SGC7901 细胞系中，过表达 S100P 的细胞中 MDR1 等化疗耐药基因的 mRNA 减少，而 S100P 下调的细胞中则增加。过表达 S100P 的细胞内铂的积累增加，而 S100P 下调的细胞则减少。