The Study Of Polyphylfins â…¦ On The Inhibition Of Proliferation Of Cisplatin-resistant Lung Adenocarcinoma Cell A549/DDP

In the world, cancer Incidence and mortality rates showed an increasing trend. Cancerhas become the “killer” following the cardiovascular disease, which is a serious hazard tohuman health. Currently, the primary means for tumor treatment are surgery, chemotherapy,radiotherapy, biological therapy, endocrine therapy, Chinese medicine treatment,hyperthermia and radiofrequency ablation therapy and so on. As the tumor traditionaltreatment modalities, chemotherapy plays an important role, but a serious impact on the playof the efficacy of chemotherapy with the tumor cells resistance to chemotherapy drugincreasingly and appear quickly, so resistance to chemotherapy is the main reason for thefailure of chemotherapy in cancer patients. The resistance of tumor cells can be divided intoprimary resistance and acquired drug resistance. According to the different resistancespectrum, acquired drug resistance can also be divided into primary drug resistance andmultidrug resistance (MDR). The molecular mechanism of tumor cell resistance is verycomplex, in addition to the decrease of intracellular drug concentration in tumor cells, thetarget gene mutation, amplification, DNA break repair to accelerate, the anti/pro-apoptoticgene expression differences can lead to tumor cell resistance.Lung cancer is a disease in the fastest growth rate of the morbidity and mortality in theworld today, and ranks the forefront of cancer mortality. According to statistics, NSCLCaccounts for80%to85%of the total incidence of lung cancer. In these NSCLC patient whois diagnosised of more than phase III accounted for greater than40%. Chemotherapy playsan important role in the treatment of inoperable NSCLC patients. In clinical, cisplatin iscommonly used in the treatment of lung cancer, and the effectiveness of its anti-tumor hasbeen fully recognized. But cisplatin can easily form a resistance, including innate resistanceand acquired resistance, which greatly limits the clinical application of cisplatin. Lungresistance is related to the expression of lung resistance-related genes, the most mature studyin the present is the expression of P-gp, MRP, LRP, GST-π, TOPO Ⅱα and mutant P53protein. To Study Of lung cancer resistance mechanisms, and look for the anti-cancer drugswhich not only can effectively overcome the resistance of lung cancer cells but also littledrug side effects, have become the hotspot of current research on chemotherapy.Because of little drug side effects and some anti-tumor effects, a lot of traditional Chinese herbal medicine have become an increasing concern to the researchers. RhizomaParidis has anti-tumor effect, which is a common used drug in Chinese medicine anti-cancerformulation, its application for more than a thousand years in history. Experiment has beenproved, the Rhizoma Paridis extracted by water, methanol and ethanol have significantinhibitory effect on human lung adenocarcinoma A549, human colon adenocarcinoma HT-29,human breast cancer MCF-7, human renal carcinoma A-496, human pancreatic cancerPACA-2, human prostate cancer PC-3and other variety of human tumor cells. Polyphyllinsis the main active ingredient in Rhizoma Paridis. In this experiment, the cisplatin-resistanthuman lung adenocarcinoma A549/DDP cell lines as the research object, Observe theInhibition of proliferation, and the impact on its apoptosis and cell cycle phase distribution toA549/DDP cell of the polyphyllins Ⅶ. It is designed to further explore the mechanism andprovide experimental basis for polyphyllins VII used in clinical to overcome lung cancercisplatin-resistant.METHODS:The Inhibition rate of A549/DDP cells in different concentrations ofPolyphyllins Ⅶ and different time were measured by MTT assay; After A549/DDP cellswere treated by Polyphyllins Ⅶ,Cell cycle phase distribution analysis and apoptosis ratewere detected by flow cytometry.RESULTS:A549/DDP cells were significantly inhibited by Polyphyllins Ⅶ,and theinhibitory effect was shown in the dose-dependent manners (P<0.05).With the time longerthe inhibition rate higher, the inhibition of48h and72h group was significantly increasedcompared to24h group(P<0.05), but72h group compared to48h group P>0.05, nosignificant. After24h treatment with Polyphyllins Ⅶ of50μmol/L and100μmol/L, theproportion of early apoptotic cells was significantly increased compared to the negativecontrol group with flow cytometry analysis, and with Polyphyllins Ⅶ of10,20,50μmol/L,cell cycle analysis showed G2phase arrest.CONCLUSION:Polyphyllins Ⅶ exerts inhibitory effects on proliferation of humanlung adenocarcinoma A549/DDP cells in dose-dependent manners, and have correlation withtime. Polyphyllins Ⅶ can cause the proportion of early apoptotic cells increased, ansignificantly affect the A549/DDP cell cycle phase distribution, cells were arrested in the G2phase.