Expression Of Metallothionein1H And Its Role In Drug Resistance In Advanced Non-Small Cell Lung Cancer

Background and Aim Lung cancer is one of the most common malignant tumors in todays words and the leading cause of cancer-related death. Non-small-cell lung cancer accounts for80% of lung cancer. Chemotherapy is one of the main treatments. Recent years, Platinum-based adjuvant chemotherapy improved effectively patients outcomes but the treatment often fails and limits the wide use of Cisplatin because of the development of the drug resistance. Accordingly,how to improve the sensitivity of chemotherapy drugs, reduce side effects and improve the curative effect is one of the most key problems.Metallothioneins(MTs) are a groups of ubiquitous low molecular mass,cysteine-rich intracellular metal-binding proteins. MTs are involved in trace metal homeostasis and metabolism,the detoxification of toxic metals,scavenging of free radicals. Recent years,the relationships between MT and tumors became a center of research. MTs are known to play putative roles in cancer cell proliferation,apoptosis,differentiation,drug resistance and prognosis. MTs may involve at least 10 identified functional genes: MT-1A,MT-1B,MT-1E,MT-1F,MT-1G,MT-1H,MT-1X,MT-2A,MT-3,MT-4.Researchs revealed different MTs in humans possibly play different functional roles during development or under various physiological conditions. MT isoforms may have unique functions. The expression of MT1H in blood were detected by RT-PCR,and NSCLC before and after chemotherapy are investigated to explore the relationship with Cisplatin resistance.Methods From May 2006 to September 2006, 40 pathologically confirmed advanced NSCLC patients were included. All patients received Cisplatin contained regimen chemotherapy as the first line treatment. Using RT-PCR to detect the expression of MT1H in blood from 40 cases with untreated advanced NSCLC before and after chemotherapy,and to compare MT1H expression before and after chemotherapy; All patients were divided into efficacy and inefficacy based on curative effect, and to compare MT1H expression before and after chemotherapy in both groups.Results The differences of expression of MT1H in blood before and after chemotherapy were significant(t= -4.051, P<0.05); The differences in both groups before and after chemotherapy were not significant(t =-1.145, P>0.05);The expression of MT1H was correlated with histological grades and lymph node metastasis. The differences were significant, P<0.05.Conclusions 1 MT1H expression in peripheral blood was not associated with response before chemotherapy. This suggested MT1H was associated with not intrinsic resistance in advanced NSCLC.2 MT1H leves were elevated after chemotherapy and associated with response. This suggested MT1H was associated with acquired Cisplatin—resistance in advanced NSCLC.3. As the expression of MT1H was correlated with histological grades and lymph node metastasis, the MT1H determined is of significance to direct chemistry scheme.4. Whether over- expression of MT1H can be used as a molecular mark of Cisplatin resistance in advanced NSCLC need further study.