In Vitro Study Of Human Telomerase Reverse Transcriptase MRNA Expression Predicts Chemosensitivity In Non-Small Cell Lung Cancer

BACKGROUNDAs the morbidity and fatality rate of lung cancer increased dramatically in the past two decades, the current mortality of lung cancer has become one of the major human cancers. It's morbidity and fatality rate have been among the first in a variety of the malignant tumors.According to the statistics, the mortality of lung cancer in China is in the first place in men,while in the second place in women. Every year the people who died from lung cancer, is more than the total of the patients died from breast cancer, prostate cancer and colon cancer. We need a more direct, safe and effective way to treat the disease. The current prefered treatment for lung cancer is surgical treatment, meanwhile taken radiotherapy, chemotherapy and other therapies including gene therapy and so on.With the more anticancer drugs developed,the improved methods and the accumulating clinical experience,chemotherapy has become one of the most important means in oncotherapy.Using chemotherapy for stageâ…¡,â…¢,â…£non-small cell lung cancer (NSCLC) is supprted by ACCP.Drug resistance is a mojor cause of treatment failure. Because conventional clinical and pathologic parameters cannot be used to accurately predict the response to pharmacological treatment, there exists a great need to identify new markers with which to define the subset of patients who will respond to therapy, especially the patrints suffered surgery.Human telomerase reverse transcriptase (hTERT) is a catalytic subunit, which plays a key role in the mechanism regulating telomerase activity. hTERT, human telomerase RNA ( hTR) and telomerase protein 1 (hTEP1) constitute the human telomerase.The expression of hTERT is thought to have important prognostic significance in different forms of human malignancies, and become an ideal target for oncotherapy.OBJECTIVEThrough the in vitro study of lethal effects of GCV and 5-FU, to evaluate whether the expression of the human telomerase reverse transcriptase (hTERT) mRNA, is predictive of response to chemotherapy in the non-small cell lung cancer (NSCLC) patients, and offer experimental data for the clinical trial.METHODS1. Cell growth and proliferation capacity were measured by WST-1.2. Use the WST-1 to detect the lethal effect of A cell and B cell with single or combine medication.3. Through the real-time PCR to determine the relatively quantitate of hTERT gene.RESULTS1. To the A and B cells ,the 5-FU and GCV have the significant cytoxicity, with the inhibitory concentration 50 (IC₅₀) of 48.8563μg/ml, 307.8625μg/ml and 47.4537μg/ml,704.4312μg/ml, respectively. Combine the 5-FU and GCV has the significant synergetic effect. The coeffeicient of drug interaction (CDI) was lower than 1.2. The expression of hTERT mRNA was significant suppressed by the anticancer drugs. (P < 0.05)3. A positive correlation (P < 0.05) was seen between the inhibition rate of hTERT mRNA and the dosage of 5-FU.4. While the dosage of GCV from 100 to 1600μg/ml, the expression of hTERT mRNA in A and B cells were constant.CONCLUSION1. The 5-FU and GCV have the significant cytoxicity,and it seems to be a dose-dependent.2. A positive correlation was seen between the inhibition rate of hTERT mRNA and the dosage of 5-FU.3. hTERT might be a independent prediction for chemotherapy in NSCLC.