本文關鍵詞：紫草素對甲狀腺腫瘤惡性行為的影響及其分子機制研究　出處：《西安交通大學》2017年博士論文　論文類型：學位論文

  更多相關文章： 甲狀腺腫瘤 紫草素 PI3K/Akt通路 MAPK通路 p16/Rb通路 活性氧產物

【摘要】：研究背景:甲狀腺癌是內分泌系統(tǒng)最常見的惡性腫瘤,雖然80%以上的甲狀腺腫瘤屬高分化癌,通過手術及放射碘治療,預后較好。但甲狀腺腫瘤存在容易復發(fā)的特點,并存在病情進展為低分化或未分化癌的風險,分化差的甲狀腺腫瘤手術及放化療效果均不佳,生存率極低。因此,臨床仍需尋找安全有效的內科治療藥物,以彌補現(xiàn)有治療方案的缺陷。紫草素提取自中藥紫草根,是一種萘醌類活性成分。紫草在傳統(tǒng)中醫(yī)應用于活血涼血、利大小腸、治療斑疹不透、水火燙傷等�，F(xiàn)代醫(yī)學發(fā)現(xiàn)紫草素具有抗炎、滅病原微生物、抗血小板、抗癌等多種功效。其中抗癌功效已分別在直腸癌、黑色素瘤、白血病、乳腺癌以及肝癌等多種腫瘤中得以證實。但是,仍缺乏紫草素在甲狀腺腫瘤治療中的應用及研究報道。研究目的:本研究旨在揭示紫草素對甲狀腺腫瘤生物學行為的影響,并揭示紫草素的抗癌機制。實驗設計:本研究分別設計相應實驗,檢測紫草素對甲狀腺腫瘤細胞的增殖、周期、凋亡、遷移及侵襲的影響,并構建裸鼠皮下移植瘤模型,檢測紫草素在體內對甲狀腺腫瘤細胞的作用,并通過檢測細胞內各信號分子的含量及活性研究紫草素對腫瘤信號分子的調節(jié)作用。實驗結果:本研究實驗發(fā)現(xiàn)紫草素能夠有效抑制甲狀腺腫瘤細胞增殖,并呈良好的時間及劑量依賴關系。紫草素能夠誘導甲狀腺腫瘤細胞周期抑制及細胞凋亡,其中凋亡的誘導是通過活性氧產物(ROS)介導的DNA損傷及p53信號通路的激活而實現(xiàn)。同時,本研究還發(fā)現(xiàn)紫草素能夠抑制甲狀腺腫瘤細胞上皮間質轉化及Slug,MMP-2,-9 and-14的表達,從而顯著抑制細胞的遷移和侵襲。分子機制的研究還發(fā)現(xiàn)紫草素能夠明顯抑制Akt及Erk磷酸化,激活p16/Rb信號通路,并且紫草素的分子調節(jié)機制均由ROS介導完成。另外,來源于FTC133細胞的裸鼠皮下移植瘤實驗結果證實紫草素在裸鼠體內仍具有良好的抑癌效果,重要的是,具有較小的細胞毒性。結論:通過本研究,我們首次揭示了紫草素在甲狀腺腫瘤治療方面具有良好的應用前景。
[Abstract]:Background: thyroid cancer is the most common malignant tumor of endocrine system. Although more than 80% of thyroid tumors are highly differentiated cancer, surgery and radioiodine therapy are the best. But thyroid tumor has the characteristics of easy recurrence, and there is a risk of progression to poorly differentiated or undifferentiated cancer. Poorly differentiated thyroid tumors are poorly treated with surgery and radiotherapy and chemotherapy, and the survival rate is very low. Therefore, it is still necessary to find safe and effective medical treatment drugs to make up for the defects of the existing treatment. Purple grass is extracted from the root of Chinese herbal medicine purple grass, which is a kind of naphthone active component. The traditional Chinese medicine is used in traditional Chinese medicine to live blood, cool blood, make small intestine, treat macula and water fire and so on. Modern medicine has found that it has many functions, such as anti - inflammatory, pathogenic microorganism, anti - platelet and anticancer. The anti-cancer effect has been confirmed in many kinds of tumors, such as rectal cancer, melanoma, leukemia, breast cancer and liver cancer. However, there is still a lack of application and research reports on the treatment of thyroid tumors. Objective: the purpose of this study was to reveal the effects of Ara on the biological behavior of thyroid tumors and to reveal the anticancer mechanism of Ara. Study design: This study were designed experiments, effects of shikonin on the detection of thyroid cancer cell proliferation, cycle and apoptosis, migration and invasion, and construct the subcutaneous tumor model in nude mice, the detection of shikonin in effect in vivo of thyroid tumor cells, and through the study of shikonin content and activity of different signal molecules in cell detection the molecular regulation of tumor signal. The results were as follows: the results of this study showed that herb can effectively inhibit the proliferation of thyroid tumor cells, and had a good time and dose dependence. Shikonin can induce cell cycle arrest and apoptosis in thyroid cancer, and apoptosis is induced by DNA damage mediated by reactive oxygen species (ROS) and activation of p53 signaling pathway. Meanwhile, it is also found that shikonin inhibits epithelial mesenchymal transition and expression of Slug, MMP-2 and -9 and-14 in thyroid cancer cells, thereby significantly inhibiting cell migration and invasion. Molecular mechanism studies also showed that shikonin inhibited Akt and Erk phosphorylation and activated p16/Rb signaling pathway, and the molecular regulatory mechanism of shikonin was mediated by ROS. In addition, the nude mice xenograft tumor derived from FTC133 cells showed that shikonin still had good antitumor effect in nude mice, and importantly, it had less cytotoxicity. Conclusion: through this study, we have revealed for the first time that it has a good prospect in the treatment of thyroid tumor.
【學位授予單位】：西安交通大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R736.1

【參考文獻】

相關期刊論文 前1條

1 韓曉晨;;甲狀腺癌的治療進展[J];中國煤炭工業(yè)醫(yī)學雜志;2006年08期

，

本文編號：1345735