| Background & Objective: Lung cancer is the most common cancer disease, seriously endangering people’s lives and health. Based on the biological characteristics,treatment effects and prognosis of lung cancer, the World Health Organization will be divided into small cell lung cancer and non small cell lung cancer. Cancer is a systemic disease, and lung cancer is no exception. Even in the early stage of lung cancer, there may be a small metastatic tumor in the body, so the treatment of lung cancer is mainly based on the combination therapy. Over the past 10 years, the diagnosis and treatment of lung cancer has been greatly improved, but the overall prognosis of patients with lung cancer is still not ideal. In spite of stage I and II patients can be cured by surgery.However, in the actual clinical work, only 10%- 20% of the patients at the time of diagnosis belongs to the early,the vast majority of patients is advanced to be radical surgery. Platinum-based combination chemotherapy of two drugs as its main treatment,but multi-drug resistance often leads to the failure of chemotherapy. the multidrug resistance of lung cancer has been a lot of study,but the underlying mechanism remains unclear. New resesrch found that the transfer of lung resistance protein(LRP) and multidrug resistance associated protein(MRP), P-glycoprotein(P-gp) and glutathione S-transferase enzyme- pi(GST) and topoisomerase II(Topo II) play an important role in the drug resistance of tumor. Poly ADP-ribose polymerase-1 [Poly(ADP-ribose)merase-1, PARP-1] is present in most eukaryotic proteins ribozyme within the cell,which maintain genomic stability, regulate gene transcription. Our previous studies have shown that, PARP-1 expression was significantly upregulated in cisplatin-resistant lung cancer cell lines, the third generation of PARP-1 inhibitor PJ-34 can induce apoptosis, inhibition of DNA damage repair, enhancement of lung adenocarcinoma sensitivity to cisplatin-resistant cells to cisplatin. The purpose of this study is to explore the differential expression about five kinds of drug resistance related gene in lung adenocarcinoma cancer cells resistant to cisplatin and parental cells, and effect of PJ34 on the expression of drug resistance related genes, and search for genes that play a key role in the resistance to cisplatin.This will provide theoretical basis for the application of PJ34 in patients with platinum resistant non small cell lung cancer.Methods1. Cultured the human lung adenocarcinoma A549/DDP and A549 cells in vitro.MTT method was used to determine the effects of DDP on the proliferation of A549/DDP cells.2. The m RNA transcription levels of LRP, MRP, P-gp, GST-π, TOPO-Ⅱα were quantified by RT-PCR in A549/DDP and A549, then the influence of PJ34 on the expression of five kinds of multidrug resistance related gene were determined in A549/DDP cells.Results1.Compared with the parental cell line A549, cisplatin resistant cell line A549/DDP resistance index increased by 9.7 times.2.Expression of LRP, MRP and P-gp and GST, Topo IIα were discovered in A549 /DDP and A549 cells, but expression of LRP, MRP, P-gp and GST in A549 / DDP cells was significantly higher than that of A549 cell, There was no difference about TOPOIIα in two kinds of cells.3.The expression of MRP、P-gp are obviously decreased giving different dose(0、3、6、12、24 mg/L) with PJ34 treatment for 24 h in A549/DDP,and there is no obvious chance to LRP、GST-π、TOPO-Ⅱα4.The expression of MRP、P-gp were decreased gradually with the prolongation of time after 24、48、72 hour with PJ34(3 mg/L),but there are no obvious chance to LRP、GST-π、TOPO-Ⅱα5.Compared with control group,pj34 could significantly lower the level of MRP、P-gp m RNA. The same results were observed in the grop of PJ34 combine with cisplatin and cisplatin singleConclusion1. LRP, MRP, P-gp, GST-π are probably involved in secondary drug resistance of DDP in A549/DDP cells.2. PJ-34 sensitizes DNA to DDP damage by indirectly downregulating m RNA levels of MRP and P-gp. |
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