目的 探討具有"扶正解毒祛瘀"作用的中藥復(fù)方消巖湯對耐順鉑人肺腺癌A549/DDP細(xì)胞多藥耐藥基因(MDR)的表達(dá)產(chǎn)物P糖蛋白(P-gP)及其mRNA表達(dá)水平的影響。方法 選擇耐順鉑人肺腺癌A549/DDP細(xì)胞系作為獲得性耐藥模型,給予消巖湯含藥血清,采用Western Blotting 免疫印跡法及RT-PCR技術(shù)檢測MDR的表達(dá)產(chǎn)物P-gP的含量及其mRNA表達(dá)水平。結(jié)果 與對照組比較,隨著消巖湯含藥血清藥物濃度的增加,P-gP蛋白表達(dá)逐漸減弱(P<0.05);與對照組比較,經(jīng)不同濃度消巖湯含藥血清作用后,A549/DDP細(xì)胞中的MDR1基因的mRNA水平均有所下降(P<0.05),且隨著藥物濃度的增加,基因表達(dá)抑制作用越明顯。結(jié)論 消巖湯逆轉(zhuǎn)肺癌耐藥的可能機(jī)制為通過抑制細(xì)胞膜上P-gP及其基因的表達(dá)而阻止細(xì)胞對順鉑的輸出,從而聚集細(xì)胞內(nèi)的藥物濃度達(dá)到有效逆轉(zhuǎn)肺癌耐藥的效果。

Objective To study the Chinese materia medica compound (Xiaoyan Decoction) against lung adenocarcinoma A549/DDP cell multidrug resistance (MDR) in human gene expression product of P glycoprotein (P-gP) and its mRNA expression level influence, to find Xiaoyan Decoction target resistant to chemotherapy, to overcome the drug resistance in lung cancer research foundation laid. Methods The choice of model as acquired resistance to cisplatin resistance of human lung adenocarcinoma A549/DDP cell line, the application of serum pharmacology method, using Western blotting and RT-PCR technique for the detection of Xiaoyan Decoction on MDR of A549/DDP cell gene expression product of P-gP and its effect on mRNA expression level. Results Compared with the normal saline group, with the serum drug concentration of Xiaoyan Decoction increased and the expression of P-gP protein decreased gradually (P<0.05); Compared with the saline group, serum was treated with different concentration of Xiaoyan Decoction after the action of MDR1 gene in A549/DDP cells and the mRNA levels were decreased, and with the increase of drug the concentration, the more obvious inhibition of gene expression was observed (P<0.05). Conclusion The possible mechanism of Xiaoyan Decoction reversal of drug resistance in lung cancer is obtained by inhibiting the expression of P-gP on the cell membrane and its gene and the cell output to cisplatin could be prevented, thus the aggregation of the intracellular drug concentration effectively could reverse the effect of drug resistance in lung cancer.

天津市應(yīng)用基礎(chǔ)及前沿技術(shù)研究計(jì)劃(青年基金項(xiàng)目)(12JCQNJC07500);天津市高等學(xué)?？萍及l(fā)展基金計(jì)劃項(xiàng)目(20110223)