Abstract
BackgroundDrug 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.MethodsAfter 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.ResultsCompared 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.ConclusionsThe 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.
Highlights
Drug resistance remains a great challenge in the treatment of gastric cancer
L-OPH was shown to be effective in primary CDDP- and carboplatin-resistant colon carcinoma and some secondary CDDP-resistant malignant tumors [5,6,7]
Chen et al considered that the drug-resistant mechanisms of gastric cancer to L-OHP and CDDP were correlated with augmentation of DNA repair and ATP7A overexpression [8]
Summary
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. Current chemotherapy programs continue to improve, individual differences of tumor patients in the sensitivity to chemotherapeutics have led to chemotherapeutic efficacy in most patients remaining unsatisfactory. Gastric cancer is a common alimentary canal malignant tumor, which shows both primary and secondary drug resistance. Chen et al considered that the drug-resistant mechanisms of gastric cancer to L-OHP and CDDP were correlated with augmentation of DNA repair and ATP7A overexpression [8]. MDR mechanisms of gastric cancer cells were detected to aid in choosing effective anti-cancer drugs, and individualized treatment plans were made, resulting in improved gastric therapeutic effects
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