李博 姜秀秀 曹晶 李楠 张艰.自噬与非小细胞肺癌对吉非替尼耐药关系的实验研究[J].,2014,14(27):5204-5206 |
自噬与非小细胞肺癌对吉非替尼耐药关系的实验研究 |
Study on the Correlation of Autophagy with Gefitinib Resistance of Non-small-cell Lung Cancer |
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DOI: |
中文关键词: 非小细胞肺癌 吉非替尼 耐药 自噬 |
英文关键词: Non-small-cell lung cancer Gefitinib Resistance Autophagy |
基金项目:国家自然科学基金项目(81272518) |
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中文摘要: |
目的:探讨细胞自噬与非小细胞肺癌对Gefitinib 耐药的相关性,寻找逆转非小细胞肺癌对Gefitinib 耐药的新靶点。方法:以
体外培养的人非小细胞肺癌Gefitinib 敏感细胞PC-9 与Gefitinib 耐药细胞PC-9/GR为研究对象,通过MTT 法检测Gefitinib 对
PC-9 及PC-9/GR 细胞存活率的影响;Western blot检测Gefitinib 对PC-9 及PC-9/GR 细胞中自噬相关蛋白LC3 的表达的影响;流
式细胞术检测自噬诱导剂雷帕霉素和Gefitinib 对PC-9/GR 细胞凋亡率的影响。结果:PC-9/GR 细胞Gefitinib IC50为PC-9 细胞的
200倍以上,具有非常明显的耐药性。PC-9/GR 细胞中LC3II 的表达显著低于PC-9/GR 细胞(P<0.05)。Rapamycin 联合Gefitinib作
用于PC-9/GR细胞可以明显提高其细胞凋亡率(P<0.05)。结论:细胞自噬减弱与非小细胞肺癌对Gefitinib 耐药有关,诱导细胞自
噬可能逆转非小细胞肺癌对Gefitinib 耐药。 |
英文摘要: |
Objective:To explore the correlation of autophagy with gefitinib resistance of non-small-cell lung cancer and
investigate a novel approach to reverse drug resistance.Methods:Gefitinib-sensitive cell line PC-9 and Gefitinib-resistant cell line
PC-9/GR were cultured in vitro. MTT assay was applied to test the cell viabilities of PC-9 and PC-9/GR cells after gefitinib treatment.
Western blot analysis was used to determine the expression of autophagy related protein LC3. Flow cytometry was also used to measure
the apoptosis after rapamycin and/or gefitinib treatments.Results:The IC50 of PC-9/GR cells was 200-fold higher than that of PC-9 cells.
PC-9/GR cells were obviously resistant to gefitinib. The expression of LC3 protein in PC-9/GR cells was significantly lower than that of
PC-9 cells. Induction of autophagy by rapamycin reversed resistance and promoted the apoptosis in PC-9/GR cells.Conclusion:The
decrease of autophagy was associated with gefitinib resistance in lung cancer, induction of autophagy might be a novel approach to
reverse gefitinib resistance. |
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