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銀蓮花素A對卵巢癌細(xì)胞Skov3的抑瘤作用及機(jī)制研究

發(fā)布時間:2018-06-29 07:07

  本文選題:銀蓮花素A + 卵巢癌。 參考:《吉林大學(xué)》2014年碩士論文


【摘要】:卵巢癌是死亡率最高的婦科惡性腫瘤,因其發(fā)病隱匿、進(jìn)展迅速,使得70%~80%的患者發(fā)現(xiàn)時已為晚期,給臨床治療帶來較大困難。盡管人們不斷開展卵巢癌的相關(guān)研究,但其起源和發(fā)病機(jī)制至今仍未完全闡明。在卵巢惡性腫瘤中,上皮性卵巢癌(Epithelialov arianc ancer, EOC)約占90%[1,2]。有研究表明,上皮性卵巢癌不是獨立的疾病,而是一組不同的腫瘤,可以根據(jù)形態(tài)和遺傳分子特征進(jìn)行分類[3]。目前國際婦產(chǎn)科聯(lián)盟(TheInternational Federation of Gynecology and Obstetrics, FIGO)和美國國家綜合癌癥網(wǎng)(The National Comprehensive Cancer Network, NCCN)推薦的標(biāo)準(zhǔn)治療方案是腫瘤細(xì)胞減滅術(shù)輔以紫杉醇和鉑類為主的聯(lián)合化療,但由于長期化療使得腫瘤細(xì)胞對鉑類藥物產(chǎn)生耐藥從而引起復(fù)發(fā)[4,5],同時化療藥物副反應(yīng)較大,藥物價格昂貴等因素,常常導(dǎo)致化療中斷從而影響治療效果,使得卵巢癌患者五年生存率一直徘徊在40%左右[5],絕大部分患者在無瘤生存18個月后復(fù)發(fā)[6]。因此,減輕化療藥物的毒副作用、逆轉(zhuǎn)卵巢癌細(xì)胞耐藥性等問題是目前研究的熱點和難點。尋找可抑制腫瘤生長、轉(zhuǎn)移以及逆轉(zhuǎn)耐藥的純天然有效制劑就顯得尤為重要。 祖國傳統(tǒng)醫(yī)學(xué)是中華民族的精粹,中藥治療腫瘤在我國具有悠久的歷史,因中藥的抑瘤效果好、副作用小、成本低等優(yōu)點,近年來受到國際社會的關(guān)注。多被銀蓮花(A. raddeana Regel)的根莖中藥名為兩頭尖,又名竹節(jié)香附,是我國的傳統(tǒng)中藥,其具有祛風(fēng)利濕、消腫止痹之功效,可用于治療風(fēng)寒濕痹、骨節(jié)疼痛、四肢拘攣、癰腫潰爛等癥[7]。隨著現(xiàn)代藥理研究的不斷深入,,人們發(fā)現(xiàn)多被銀蓮花在消腫止痛、抗菌抑菌、免疫調(diào)節(jié)以及抗腫瘤方面具有較好的藥用價值。上世紀(jì)80年代從該藥中分離出的銀蓮花素A具有抗癌活性[8],且可能沒有誘變?nèi)旧w的副作用[9]。多被銀蓮花提取物在體內(nèi)、外均具有較好的抑瘤作用,誘導(dǎo)腫瘤細(xì)胞凋亡是其發(fā)揮抗腫瘤作用的一條重要途徑,同時還可通過調(diào)節(jié)機(jī)體免疫的機(jī)制發(fā)揮抗腫瘤作用[10]。已有學(xué)者發(fā)現(xiàn),銀蓮花素A對結(jié)腸癌、肺癌、肝癌以及宮頸癌具有明顯的抑制作用,但在卵巢癌方面的研究少見。本課題以多被銀蓮花的提取物銀蓮花素A為研究對象,探討不同濃度的銀蓮花素A單體對卵巢癌細(xì)胞Skov3增殖、凋亡及遷移、侵襲能力的影響,并通過Real time PCR檢測Bax、Caspase3、Bcl-2、Stat3、MMP-2、MMP-9、Cyclin D1基因的轉(zhuǎn)錄;Western-blot檢測Cyclin D1、Cyclin B1、Bcl-2、Cyt-c、Caspase-3、Bcl-xL、Bax、MMP-9、MMP-2、Stat3蛋白的表達(dá),探討其作用機(jī)制,為銀蓮花素A單體治療卵巢癌的臨床應(yīng)用及其進(jìn)一步開發(fā)提供理論依據(jù)。
[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.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2014
【分類號】:R737.31

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3 林小欽;李東良;楊才生;何秀華;方堅;;竹節(jié)香附素A對人肝癌細(xì)胞HepG_2增殖的抑制作用[J];現(xiàn)代藥物與臨床;2009年01期

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