肺腺癌A549/DDP细胞多药耐药机制及中药逆转剂的研究进展

肺癌是严重影响人类生存的恶性肿瘤之一,其死亡率已居全球恶性肿瘤之首。目前主要采取以化疗为主的综合治疗方案,其疗效并不理想,主要原因是肺癌细胞对化疗药物产生多药耐药性(multi-drug resistance,MDR)。近年来肺腺癌耐药发生率高于鳞癌,应用cis-dichlorodiamineplatinum(DDP)诱导建立的肺腺癌多药耐药细胞系A549/DDP具有代表性。因此深入研究肺腺癌A549/DDP细胞的MDR机制及寻找安全、有效的逆转剂则成为当务之急。文献检索研究表明,肺腺癌A549/DDP细胞多药耐药机制主要涉及膜转运蛋白介导的药物外排泵机制、酶介导的肿瘤细胞解毒和修复功能增强、凋亡调控基因异常、信号转导因子发挥抗凋亡机制、上皮-间质细胞转化(EMT)导致的免疫逃逸。针对肺腺癌A549/DDP细胞多药耐药的中药逆转剂则主要涉及中药单体、中药复方、单味中药及中药有效成分、提取复合物。现就近年来肺腺癌A549/DDP细胞多药耐药机制及中药逆转剂的研究进展作一综述。

Research Progress of Lung Adenocarcinoma A549/DDP Cells Multi-drug Resistant Mechanism and Traditional Chinese Medicine Reversal Agents

Lung cancer is one of the malignant tumors that seriously influence human survival. Its mortality rate has been among the top of the global malignant tumors. Comprehensive treatment scheme mainly with chemotherapy is generally adopted, but the curative effect is not ideal. The main reason is that the lung cancer cells produce multi-drug resistance (MDR) to chemotherapy drugs. The drug resistance incidence of lung adenocarcinoma in recent years is higher than that of squamous cell carcinomas. Multi-drug resistant cell line A549/DDP of lung adenocarcinoma induced by cis-Dichlorodiamineplatinum (DDP) is very representative. Therefore, further study of lung adenocarcinoma A549/DDP cells MDR mechanisms and looking for safe and effective reversal agents have become the urgent matter. Literature retrieval research has shown that lung adenocarcinoma A549/DDP cells multi-drug resistance mechanism mainly involves membrane transport protein-mediated drug efflux pump mechanism, enzyme-mediated tumor cells detoxification and repair enhancements, abnormal apoptosis regulation genes, antiapoptotic mechanism of signal transduction factors and immune escape caused by Epithelial-Mesenchymal transit (EMT). Reversal agents of traditional Chinese medicines aiming at lung adenocarcinoma A549/DDP cells multi-drug resistance are mainly related to traditional Chinese medicine monomer, traditional Chinese medicine compound, single Chinese medicine and its effective components, and extraction of compounds. Here we will further review lung adenocarcinoma A549/DDP cells multi-drug resistant mechanism and research progress of reversal agents in traditional Chinese medicine.