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Reverse Effect of Recombinant Human Endostatin on Drug-resistance of A549/DDP Cells to Cisplatin

Author: ZhangHongMei
Tutor: SunXiuHua
School: Dalian Medical University
Course: Oncology
Keywords: Recombinant human endostatin Lung cancer Resistance A549/DDP cell lines
CLC: R734.2
Type: Master's thesis
Year: 2009
Downloads: 87
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Abstract


BACKGROUND: Lung cancer has become the world's most common malignancy in cancer-related cause of death accounted for the first one. Current treatment of lung cancer is an integrated therapy, chemotherapy in the treatment of lung cancer has an important position, drug resistance is a major cause of failure of chemotherapy. One way to overcome drug resistance reversal agent is used in the treatment of lung cancer, DDP is the main chemotherapy drugs, easy to produce drug resistance, the impact effect of chemotherapy. Recombinant human endostatin (ex degrees Endostar) as an inhibitor of vascular endothelium, with a clear target, drug side effects, does not produce drug resistance and other characteristics, can increase the efficacy of chemotherapy in combination with chemotherapy. Endostar chemotherapy effect may be related to reversal of tumor cells to chemotherapeutic drug resistance related. This study investigated the recombinant human endostatin (ex degrees Endostar) to DDP resistance reversal effect and mechanism, to further explore the mechanism of synergistic Endostar chemotherapy. Objective: To investigate recombinant human endostatin (ex degrees Endostar) A549/DDP reversal and reversal of the occurrence of drug resistance mechanisms. Methods: In this study, human lung adenocarcinoma cell line A549 and resistant cell lines A549/DDP as research subjects to DDP with Endostar their combination and a separate mode of administration were acting on the human lung adenocarcinoma cell line A549 and drug cells A549/DDP, action time 72 hours, observe the different modes of administration in the same cell lines differ between different cell lines and differences between. MTT assay was used Endostar right A549/DDP cell resistance reversal effect; using flow cytometry A549/DDP group, DDP group, Endostar and DDP group were acting on A549/DDP cells relative fluorescence intensity; RT- PCR, DDP group, Endostar and DDP group, Endostar groups were acting on cells resistant A549/DDP the mRNA expression, and the establishment of A549 cells in control group, A549/DDP cell control group, while the control group was also detected mRNA expression of resistance, detect resistance genes include: glutathione-S-transferase (GST), topoisomerase Ⅱ (TOPO-Ⅱ) and lung resistance protein (LRP). Results: 1.DDP half inhibitory concentration of A549 cells (IC50) was (0.72 ± 0.05) ug / ml, for A549/DDP half inhibitory concentration (IC50) was (11.54 ± 0.64) ug / ml. Visible, A549/DDP to DDP resistance index is 16. Endostar and DDP right A549/DDP half inhibitory concentration (IC50) was (2.0 ± 0.1) ug / ml. Reversal fold (RF) was 5.77, the relative reversal rate (RRR%) was 88.2 ℅, tips Endostar A549/DDP resistant cells with the role reversal. And DDP in A549 cells Endostar half inhibitory concentration (IC50) was approximately (0.25 ± 0.06) ug / ml, tips Endostar with DDP in vitro obvious synergy. (2) Flow cytometry showed that the fluorescence intensity DDP: DDP monotherapy group, A549/DDP control group, Endostar and DDP group relative fluorescence intensity were: 1618 ± 82.31,974 ± 13.45,2958 ± 63.96, P statistical analysis lt; 0.05, tips Endostar can increase intracellular platinum content, increase treatment efficacy. 3.RT-PCR test results showed: A549/DDP intracellular GST, TOPO-Ⅱ mRNA expression in A549 cells than high, DDP combined Endostar group treated A549/DDP intracellular GST, TOPO-Ⅱ gene mRNA significantly decreased the expression of each group were P <0.05, statistically significant. Cells in each group were LRP expression, A549/DDP cells compared with A549 cells expressing high LRP by Endostar and DDP treatment, A549/DDP cells slightly decreased expression of LRP, each group were P gt; 0.05, not statistically significant. Conclusion: Endostar A549/DDP can reverse resistance to DDP, Endostar reversal DDP resistance mechanism may be reduced A549/DDP intracellular GSH and TOPO-Ⅱ mRNA expression, an increase of intracellular containing A549/DDP the amount of platinum.

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CLC: > Medicine, health > Oncology > Respiratory system tumors > Lung tumors
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