CIK 联合奥沙利铂对人奥沙利铂耐药胃癌细胞的体内外抗肿瘤作用。

Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro.

机构信息

Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

J Exp Clin Cancer Res. 2010 Aug 30;29(1):118. doi: 10.1186/1756-9966-29-118.

DOI:10.1186/1756-9966-29-118

PMID:20799994

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2939545/

Abstract

BACKGROUND

Drug resistance remains a great challenge in the treatment of gastric cancer. The goal of this study was to explore the anti-tumor effects and mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP) in human oxaliplatin-resistant gastric cancer cells.

METHODS

After producing oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling time were observed, followed by detection of cell cycle distribution and apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT assay, in vivo pharmacodynamics and pathomorphology experiments were used to detect killing activities of CIK combined with L-OHP.

RESULTS

Compared with parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S phase were reduced and cell apoptosis rate was increased (P < 0.05), the inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer cells was significantly lower and the expression of P-gp was significantly higher (P < 0.05). However, there was no significant difference in livin expression between parental gastric cancer cells and oxaliplatin-resistant gastric cancer cells (P > 0.05). The in vitro killing activity of CIK combined with L-OHP on parental cells and oxaliplatin-resistant cells were significantly enhanced compared with L-OHP or CIK alone. And it showed greater synergetic effects against oxaliplatin-resistant cells compared with parental cells (P < 0.05). In addition, survival rate, abdominal circumference and pathomorphology results revealed stronger in vivo anti-tumor effects when the two therapies were combined.

CONCLUSIONS

The mechanism of oxaliplatin-resistant cell secondary multidrug resistance was correlated with the variation of cell cycle distribution, extension of doubling time and upregulation of P-gp expression. The synergistic effect of CIK in combination with L-OHP on killing activity against oxaliplatin-resistant cells was shown in vivo and in vitro.

摘要

背景

耐药性仍然是胃癌治疗的一大挑战。本研究旨在探讨细胞因子诱导的杀伤（CIK）细胞联合奥沙利铂（L-OHP）对人奥沙利铂耐药胃癌细胞的抗肿瘤作用及其机制。

方法

在产生奥沙利铂耐药胃癌细胞后，观察细胞形态、生长和倍增时间，检测细胞周期分布和凋亡，药物敏感性（如 L-OHP）和 P-糖蛋白和 livin 的表达。MTT 测定、体内药效学和病理形态学实验用于检测 CIK 联合 L-OHP 的杀伤活性。

结果

与亲本胃癌细胞相比，奥沙利铂耐药胃癌细胞 S 期减少，细胞凋亡率增加（P<0.05），10 种化疗药物对奥沙利铂耐药胃癌细胞的抑制率明显降低，P-糖蛋白表达明显升高（P<0.05）。然而，亲本胃癌细胞和奥沙利铂耐药胃癌细胞 livin 表达无明显差异（P>0.05）。与 L-OHP 或 CIK 单独作用相比，CIK 联合 L-OHP 对亲本细胞和奥沙利铂耐药细胞的体外杀伤活性明显增强。并且对奥沙利铂耐药细胞的协同作用大于亲本细胞（P<0.05）。此外，两种治疗方法联合应用时，存活率、腹围和病理形态学结果显示出更强的体内抗肿瘤作用。

结论

奥沙利铂耐药细胞继发多药耐药的机制与细胞周期分布的变化、倍增时间的延长和 P-糖蛋白表达的上调有关。CIK 联合 L-OHP 对奥沙利铂耐药细胞的杀伤活性具有协同作用，无论是在体内还是体外。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9dd/2939545/0e1633cc942c/1756-9966-29-118-1.jpg

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CIK 联合奥沙利铂对人奥沙利铂耐药胃癌细胞的体内外抗肿瘤作用。

Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro.

机构信息

Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.