| 引用本文:郝雨1，朱宝琛2，薛春苗1，2，华国栋2，高若瑜1，黄鑫2，刘文卉1，王萌2.基于P糖蛋白研究仙茅对顺铂耐药非小细胞肺癌细胞的增敏机制[J].世界中医药,2022,(24):. |
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| 基于P糖蛋白研究仙茅对顺铂耐药非小细胞肺癌细胞的增敏机制 |
| Sensitivity-enhancing Mechanism of Curculiginis Rhizoma in Cisplatin-resistant Non-small Cell Lung Cancer Cells Based on P-glycoprotein |
| 投稿时间：2022-05-21 |
| DOI：10.3969/j.issn.1673-7202.2022.24.006 |
| 中文关键词: 仙茅 苔黑酚葡萄糖苷 非小细胞肺癌 肺癌耐药细胞 P糖蛋白 顺铂 多药耐药 ATP结合盒 |
| English Keywords:Curculiginis Rhizoma Orcinol glucoside Non-small cell lung cancer Drug-resistant lung cancer cells P-glycoprotein Cisplatin Multidrug resistance ATP-binding cassette |
| 基金项目:国家自然科学基金青年科学基金项目(82004125)；北京中医药大学东直门医院2020科技创新专项(DZMKJCX-2020-004) |
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| 中文摘要: |
| 目的：探究中药仙茅水煎液及其主要入血成分苔黑酚葡萄糖苷(OG)对非小细胞肺癌(NSCLC)顺铂耐药细胞(A549/cis)耐药性的影响及其潜在机制。方法：用AutoDock Vina分子对接软件评估P糖蛋白(P-gp)与OG的结合能力；CCK-8法检测顺铂、仙茅水煎液、OG及其联用对A549/cis细胞活力的抑制率；蛋白质免疫印迹法检测A549/cis中P-gp的表达水平。结果：P-gp与OG模拟分子对接的结合自由能为-7.6 kcal/mol（1 cal=4.184 J），二者具有良好的结合活性；顺铂对A549/cis的半抑制浓度(IC50)约为5.5 μg/mL，仙茅水煎液与OG在梯度浓度下对A549/cis活力均无明显影响；顺铂低剂量(1.5 μg/mL)与仙茅水煎液高、低剂量(1 000 μg/mL、500 μg/mL)或OG高剂量(5×10-5mol/L)联用组、顺铂中剂量(4 μg/mL)与仙茅水煎液高、低剂量(1 000 μg/mL、500 μg/mL)或OG高、低剂量(5×10-5mol/L、1×10-5mol/L)联用组较顺铂单用组细胞抑制率均显著升高(P<0.05或P<0.01)；顺铂(1.5 μg/mL)与仙茅水煎液(1 000 μg/mL)或OG(5×10-5 mol/L)联用组A549/cis细胞的P-gp表达水平均低于顺铂单用组，其中顺铂与仙茅水煎液联用组降低显著(P<0.05)。结论：中药仙茅水煎液及OG均可以降低A549/cis细胞的耐药性，其增敏机制可能与抑制P-gp表达有关。 |
| English Summary: |
| To explore the effects and underlying mechanism of Curculiginis Rhizoma decoction and orcinol glucoside(OG)，the main plasma component，on cisplatin-resistant cells(A549/cis) in non-small cell lung cancer(NSCLC).Methods:The binding affinity of OG to P-glycoprotein(P-gp) was evaluated by AutoDock Vina.CCK-8 assay was used to detect the cell viability inhibition rate of cisplatin，Curculiginis Rhizoma decoction，OG，and their combination on A549/cis cells.The P-gp expression level in A549/cis cells was detected by Western blot.Results:The binding energy of simulated molecular docking of OG to P-gp was -7.6 kcal/mol(1 cal=4.184 J)，indicating that they had good binding activity.The half-maximal inhibitory concentration(IC50) of cisplatin on A549/cis cells was about 5.5 μg/mL.Curculiginis Rhizoma decoction or OG in the gradient concentrations showed no significant effect on the viability of A549/cis cells.The cell inhibition rates in drug combination groups［low-dose cisplatin(1.5 μg/mL) combined with high-and low-dose Curculiginis Rhizoma decoction(1 000 and 500 μg/mL) or high-dose OG(5×10-5 mol/L)，and medium-dose cisplatin(4 μg/mL) combined with high-and low-dose Curculiginis Rhizoma decoction(1 000 and 500 μg/mL) or high-and low-dose OG(5×10-5 and 1×10-5 mol/L)］ were higher than that in the cisplatin group(P<0.05 or P<0.01).The P-gp expression levels of A549/cis cells in groups of cisplatin(1.5 μg/mL) combined with Curculiginis Rhizoma decoction(1 000 μg/mL) or OG(5×10-5 mol/L) were both lower than that of the cisplatin group，and P-gp expression level in the group of cisplatin combined with Curculiginis Rhizoma decoction lowered significantly(P<0.05).Conclusion:Curculiginis Rhizoma decoction and OG can both reduce the drug resistance of A549/cis cells，and the sensitivity-enhancing mechanism may be related to the inhibition of P-gp expression. |
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