白術(shù)內(nèi)酯-1通過(guò)JNK-pSmad3L-c-Myc信號(hào)通路在體內(nèi)和體外抗膽囊癌活性研究
本文選題:白術(shù)內(nèi)酯-1(ATR-1) 切入點(diǎn):膽囊癌 出處:《山西醫(yī)科大學(xué)》2017年碩士論文 論文類型:學(xué)位論文
【摘要】:目的:膽囊癌發(fā)病率居消化系統(tǒng)第六位,是最頻繁多見(jiàn)的膽道惡性腫瘤,侵襲程度高,預(yù)后差。從白術(shù)中提取的白術(shù)內(nèi)酯-1(ATR-1)作為一種在中國(guó)廣泛使用的中草藥,在膀胱癌等多種腫瘤細(xì)胞中表現(xiàn)出潛在的抗腫瘤活性。然而,很少見(jiàn)白術(shù)內(nèi)酯-1對(duì)膽囊癌細(xì)胞的研究文獻(xiàn)報(bào)道。本研究的目的主要是探討ATR-1對(duì)膽囊癌細(xì)胞(NOZ和EHGB-1細(xì)胞)的增殖影響以及其潛在的分子機(jī)制,為ATR-1可能作為新型抗膽囊癌化療藥物提供實(shí)驗(yàn)數(shù)據(jù)和支撐。方法:在本次研究中,我們通過(guò)MTT、克隆形成實(shí)驗(yàn)研究了ATR-1對(duì)膽囊癌細(xì)胞株NOZ和EHGB-1細(xì)胞的增殖效應(yīng),使用Annexin-V/PI雙重染色實(shí)驗(yàn)、Hoechest33342染色實(shí)驗(yàn)探討ATR-1對(duì)膽囊癌細(xì)胞株的凋亡效應(yīng)以及流式細(xì)胞學(xué)研究細(xì)胞周期實(shí)驗(yàn),并采用Western blotting實(shí)驗(yàn)研究了ATR-1發(fā)揮抗膽囊癌作用的潛在分子機(jī)制;同時(shí)采用裸鼠負(fù)荷實(shí)驗(yàn)探討了ATR-1對(duì)體內(nèi)膽囊癌的抑制作用。結(jié)果:ATR-1根據(jù)劑量依賴方式促進(jìn)NOZ和EHGB-1的凋亡、誘導(dǎo)周期趨于阻滯在G0/G1期,從而對(duì)膽囊癌細(xì)胞發(fā)生抗增殖效應(yīng)。在裸鼠負(fù)荷瘤實(shí)驗(yàn)中,相比空白對(duì)照組,ATR-1藥物濃度越大(在安全范圍內(nèi)),裸鼠皮下移植瘤的體積和重量越小。結(jié)論:ATR-1在體內(nèi)和體外均能抑制膽囊癌細(xì)胞增殖,發(fā)揮抗腫瘤效應(yīng),有望成為膽囊癌輔助化療中的新型藥物。
[Abstract]:Objective: the incidence of gallbladder carcinoma is ranked 6th in the digestive system. It is the most frequent malignant tumor of the biliary tract, with high invasion and poor prognosis. Atractylodes macrocephala-1 ATR-1 extracted from macrocephala is widely used as a Chinese herbal medicine in China. It shows potential antitumor activity in many kinds of tumor cells, such as bladder cancer. However, The present study is to investigate the effect of ATR-1 on the proliferation of gallbladder cancer cells (Noz and EHGB-1 cells) and its potential molecular mechanism. Methods: in this study, we studied the effect of ATR-1 on the proliferation of NOZ and EHGB-1 cells. Annexin-V/PI double staining and Hoechest33342 staining were used to investigate the apoptotic effect of ATR-1 on gallbladder cancer cell line and the cell cycle test by flow cytometry. The potential molecular mechanism of ATR-1 's anti-gallbladder carcinoma was studied by Western blotting assay. The inhibitory effect of ATR-1 on gallbladder carcinoma in vivo was also investigated by using nude mice load test. Results: the apoptosis of NOZ and EHGB-1 was promoted by the dose dependent manner, and the induced cycle tended to be blocked at the G _ 0 / G _ 1 phase. Thus, the anti-proliferative effect on gallbladder cancer cells was observed in nude mice. Compared with the blank control group, the higher the concentration of ATR-1 was (within the safe range), the smaller the volume and weight of the tumor. Conclusion: in vivo and in vitro, the proliferation of gallbladder cancer cells can be inhibited and the antitumor effect of the tumor can be played by the control group. It is expected to be a new drug in adjuvant chemotherapy for gallbladder carcinoma.
【學(xué)位授予單位】:山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R735.8
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