| 毒胡萝卜素联合吉非替尼改善人肺腺癌细胞PC9/GR的耐药性研究 |
| 投稿时间：2022-09-07 修订日期：2023-06-28 点此下载全文 |
| 引用本文：杜江源,张兰林,蔡同凯,曹永兵.毒胡萝卜素联合吉非替尼改善人肺腺癌细胞PC9/GR的耐药性研究[J].药学实践杂志,2024,42(3):121~126 |
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| 基金项目:上海市虹口区卫健委面上项目（虹卫2002-02） |
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| 中文摘要:目的 研究毒胡萝卜素（thapsigargin）联合吉非替尼（gefitinib）对人肺腺癌耐药细胞株PC9/GR增殖的影响并探讨可能的机制。方法 吉非替尼单独用药或吉非替尼与毒胡萝卜素联合应用，通过CCK8实验检测上述两组药物对PC9/GR细胞增殖的影响；应用流式细胞术鉴定两组药物对PC9/GR细胞凋亡的影响；应用Western blotting法检测两组药物对PC9/GR细胞蛋白ATF-6和IRE1α表达的影响。结果 细胞增殖实验显示，与吉非替尼单独用药相比，联合用药组中PC9/GR的增殖受到更强的抑制作用；凋亡实验显示，相较于吉非替尼单独用药，联合用药能够进一步促进细胞的凋亡；Western blotting法显示，与吉非替尼单独用药相比，联合用药后PC9/GR中ATF-6和IRE1α蛋白（内质网应激标志物）表达上调，其差异具有统计学意义。结论 在毒胡萝卜素诱导下，PC9/GR细胞对吉非替尼的敏感性增加，其中机制可能与内质网应激有关。 |
| 中文关键词:吉非替尼 毒胡萝卜素 肿瘤耐药 凋亡 内质网应激 |
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| Improvement of gefitinib-resistance of PC9/GR by thapsigargin combined with gefitinib |
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| Abstract:Objective To study the effect and mechanism of the thapsigargin combined with gefitinib on the proliferation of human lung adenocarcinoma gefitinib resistance cell line PC9/GR. Methods The cell viability of PC9/GR treated with gefitinib alone or gefitinib combined with thapsigargin was evaluated by CCK8 assay. The flow cytometry was used to analyze the PC9/GR cell apoptosis indued by the two group drugs. The ATF-6 and IRE1α protein expression of PC9/GR cells treated with the two group drugs were detected by Western blotting. Results The group of drug combination exhibited enhanced ability to inhibit cell proliferation, promote cell apoptosis and upregulate the ATF-6 and IRE1α protein expression of the PC9/GR compared with the group gefitinib used alone. Conclusion The sensitivity of PC9/GR to gefitinib was increased when the cells were treated by thapsigargin, which may be related with the state of endoplasmic reticulum stress（ERS） induced by thapsigargin. |
| keywords:gefitinib thapsigargin tumor drug resisdance apoptosis endoplasmic reticulum stress |
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