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A Survey On The Mechanism Of A New Antitumor Drug TNBG With Novel Configuration

Posted on:2006-07-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:L J LiFull Text:PDF
GTID:1104360155951109Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Cancer is still a great threat to the health of human beings. According to the statistics from WHO, 10 million new cancer cases were diagnosed in 2000, and 6.2 million patients were died of cancer over the world every year. In 2000, 1.8~2.0 million cancer patients were diagnosed in china, moreover 1.4~1.5 million cancer patients died of it. At present, cancer has become the first cause of mortality in the urban population, among which lung cancer,liver cancer,gastric cancer,colon cancer, uterine cervix cancer, breast cancer, nasopharyngeal cancer,lymphoma and leukemia are most frequent and severe, so all of them became the focus of the cancer treatment and prevention in our country. Nowadays, there are four major methods used to treat cancer patients, i.e. surgery,radiation,chemotherapy,biotherapy. In the early of 1940s, scientists had found that nitrogen mustard was effective in the treatment of leukemia, and then chemotherapy had got outstanding achievements. Ever since then people paid more and more attention to chemotherapy. It's a common practice that chemotherapy has some advantages as following: firstly, it can cure a certain tumors as eradicative means; secondly, as an auxiliary means, it can kill remaining cancer cells and micro-metastasis which surgery and radiation can't do; at last, it can prolong patients' life span and improve their life quality as palliative treatment. On the other hand, the traditionary chemotherapy focused on killing cancer cells through cytotoxicity, it had some disadvantages, such as low selectivity,intense side effects,little effect on solid tumors,drug-resistances, etc. To some extent, it restricted the broad application of chemotherapy. With the increasing knowledge research on the metabolism of cancer, the focus and hot spot of research on antitumor drug has changed from traditional cytotoxic antitumor drug to new mechanism-oriented non-cytotoxic drug. It is hoped that breakthrough on cancer treatment may be achieved in the future. TNBG is a novel chemically synthesised antitumor drug. Many experiments, both in vivo and in vitro, have proved its significant antitumor effects. Moreover, TNBG could prolong the life of tumor-loading animals, and have no crossed drug-resistance, so it has a good prospect of application. And it has obtained a Chinese patent from 2001. Therefore, it is essential to do some further research on its antitumor mechanism and targets, which would provide theoretical support to develop new antitumor drugs and their derivatives. So we selected the human hepatocellular carcinoma cell line QGY-7701 as a tumor model to investigate the antitumor mechanism of TNBG. Observing the morphological changes, signal transduction pathways and different gene expressions, we proposed that the new non-cytotoxic antitumor mechanism of TNBG is related with the interference of lipid metabolism in QGY-7701 cells. And we observed the mechanism of death of cancer cells related with the above interference. The results and conclusions are as follows. 1. Antitumor effects on QGY-7701 in vitro. MTT assay and the 3H-TdR incorporation experiment were used to test its impacts on proliferation of QGY-7701.MTT assay found that the inhibition of QGY-7701 cells exposed to TNBG at a series concentration of 1μg/ml ,2μg/ml,4μg/ml and 8μg/ml for 72h were concentration dependent, and the inhibition ratios were 29.13%,43.70%, 56.96% and 86.62%,respectively. And the IC50 for 72h was 3.228μg/ml. 3~H-TdR incorporation experiment revealed that QGY-7701 cells exposed to TNBG at 4μg/ml for 72h showed an inhibition ratio of 51.79%. It turned out that TNBG could inhibit the proliferation of cancer cells. Both experiments had proved that TNBG had antitumor effects in vitro. 2. Morphological observation: Under inverted microscope, we observed that the cultured QGY-7701 cells exposed to TNGB at 4μg/ml for 72h had a large quantity of granules in the cytoplasm. Under light microscope, we found a lot of lipid droplets stained as orange by oil red O which were accumu...
Keywords/Search Tags:TNBG, antitumor drug, mechanism, lipid metabolism, lipid droplets, cell cycle, apoptosis
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