银莲花素A对卵巢癌细胞Skov3的抑瘤作用及机制研究

发布时间：2018-06-29 07:07

本文选题：银莲花素A + 卵巢癌　；参考：《吉林大学》2014年硕士论文

【摘要】：卵巢癌是死亡率最高的妇科恶性肿瘤，因其发病隐匿、进展迅速，使得70%~80%的患者发现时已为晚期，给临床治疗带来较大困难。尽管人们不断开展卵巢癌的相关研究，但其起源和发病机制至今仍未完全阐明。在卵巢恶性肿瘤中，上皮性卵巢癌(Epithelialov arianc ancer, EOC)约占90%[1,2]。有研究表明，上皮性卵巢癌不是独立的疾病，而是一组不同的肿瘤，可以根据形态和遗传分子特征进行分类[3]。目前国际妇产科联盟（TheInternational Federation of Gynecology and Obstetrics, FIGO)和美国国家综合癌症网（The National Comprehensive Cancer Network, NCCN)推荐的标准治疗方案是肿瘤细胞减灭术辅以紫杉醇和铂类为主的联合化疗，但由于长期化疗使得肿瘤细胞对铂类药物产生耐药从而引起复发[4,5]，同时化疗药物副反应较大，药物价格昂贵等因素，常常导致化疗中断从而影响治疗效果，使得卵巢癌患者五年生存率一直徘徊在40%左右[5]，绝大部分患者在无瘤生存18个月后复发[6]。因此，减轻化疗药物的毒副作用、逆转卵巢癌细胞耐药性等问题是目前研究的热点和难点。寻找可抑制肿瘤生长、转移以及逆转耐药的纯天然有效制剂就显得尤为重要。祖国传统医学是中华民族的精粹，中药治疗肿瘤在我国具有悠久的历史，因中药的抑瘤效果好、副作用小、成本低等优点，近年来受到国际社会的关注。多被银莲花(A. raddeana Regel)的根茎中药名为两头尖，又名竹节香附，是我国的传统中药，其具有祛风利湿、消肿止痹之功效，可用于治疗风寒湿痹、骨节疼痛、四肢拘挛、痈肿溃烂等症[7]。随着现代药理研究的不断深入，，人们发现多被银莲花在消肿止痛、抗菌抑菌、免疫调节以及抗肿瘤方面具有较好的药用价值。上世纪80年代从该药中分离出的银莲花素A具有抗癌活性[8]，且可能没有诱变染色体的副作用[9]。多被银莲花提取物在体内、外均具有较好的抑瘤作用，诱导肿瘤细胞凋亡是其发挥抗肿瘤作用的一条重要途径，同时还可通过调节机体免疫的机制发挥抗肿瘤作用[10]。已有学者发现，银莲花素A对结肠癌、肺癌、肝癌以及宫颈癌具有明显的抑制作用，但在卵巢癌方面的研究少见。本课题以多被银莲花的提取物银莲花素A为研究对象，探讨不同浓度的银莲花素A单体对卵巢癌细胞Skov3增殖、凋亡及迁移、侵袭能力的影响，并通过Real time PCR检测Bax、Caspase3、Bcl-2、Stat3、MMP-2、MMP-9、Cyclin D1基因的转录；Western-blot检测Cyclin D1、Cyclin B1、Bcl-2、Cyt-c、Caspase-3、Bcl-xL、Bax、MMP-9、MMP-2、Stat3蛋白的表达，探讨其作用机制，为银莲花素A单体治疗卵巢癌的临床应用及其进一步开发提供理论依据。
[Abstract]:Ovarian cancer is the highest death rate of gynecologic malignant tumor. Because of its occult and rapid progress, the patients with 70%~80% have been found to be late and have a great difficulty in clinical treatment. Although people continue to carry out the research on ovarian cancer, their origin and pathogenesis are still not fully elucidated. Epithelial ovum in ovarian malignant tumors. Epithelialov arianc ancer (EOC) accounts for about 90%[1,2]. studies. Epithelial ovarian cancer is not an independent disease, but a group of different tumors that can be classified according to the morphological and genetic molecular characteristics of the current international union of gynaecology and Obstetrics (TheInternational Federation of Gynecology and Obstetrics,) and the United States The standard treatment recommended by The National Comprehensive Cancer Network (NCCN) is cancer cell subtraction combined with paclitaxel and platinum based combined chemotherapy, but due to long-term chemotherapy the tumor cells are resistant to platinum drugs and cause relapse [4,5], while the chemotherapeutic side reactions are large and drug prices are high. Expensive and other factors often lead to chemotherapy interruption and affect the therapeutic effect. The five year survival rate of ovarian cancer patients has been hovering around 40% [5], and most of the patients relapsed after 18 months of tumor free survival [6]., so reducing the side effects of chemotherapeutic drugs and reversing the drug resistance of ovarian cancer cells are the hot spots and difficulties of the present research. It is particularly important to find natural and effective preparations that inhibit tumor growth, metastasis and reverse drug resistance.
Traditional Chinese medicine is the essence of the Chinese nation. Traditional Chinese medicine has a long history in the treatment of tumor in our country. Because of its good effect, small side effect and low cost, Chinese traditional medicine has attracted the attention of the international community in recent years. The root of the rhizome of A. raddeana Regel is called "two heads", also known as the bamboo slub, which is the traditional Chinese medicine. It has the effect of dispelling wind and dampness, eliminating swelling and stopping arthralgia, can be used in the treatment of rheumatism and damp arthralgia, bone joint pain, limb arrest, carbuncle swelling and festering and so on. With the continuous deepening of modern pharmacological research, [7]. has been found to have good medicinal value in the fields of swelling and relieving pain, antibacterial, bacteriostasis, immune regulation and anti-tumor. In the 80s of last century, The anemone A, isolated from the drug, has anti-cancer activity [8], and it may not have the side effect of mutagenesis of chromosomes, [9]. is more than the anemone extract in the body, and it has a good tumor suppressor effect. The induction of tumor cell apoptosis is an important way to play the anti-tumor effect. [10]. has been found that anemone A has obvious inhibitory effect on colon cancer, lung cancer, liver cancer and cervical cancer, but the research on ovarian cancer is rare. This subject takes anemone anemone extract of Anemone A as the research object, and discusses the proliferation and apoptosis of different concentrations of Anemone A monomer on ovarian cancer cells and apoptosis. The expression of Bax, Caspase3, Bcl-2, Stat3, MMP-2, MMP-9, Cyclin D1 gene of Bax, Caspase3, Bcl-2, Stat3, MMP-9, Cyclin D1 gene were detected by Real PCR. It provides a theoretical basis for its use and further development.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

【参考文献】