發(fā)布時(shí)間：2018-06-22 02:10

  本文選題：前列腺癌 + 微管��； 參考：《華東師范大學(xué)》2014年碩士論文

【摘要】：對(duì)于男性而言,在泌尿生殖系統(tǒng)疾病中,前列腺癌(PCa)是一種對(duì)男性健康造成極大威脅的惡性腫瘤。在美國,男性的前列腺癌新發(fā)病率占男性所有所患癌癥的第一位、其致死率則位居第二位；在中國,近些年來,隨著社會(huì)的發(fā)展,人們生活標(biāo)準(zhǔn)不斷提高、飲食方面較以往發(fā)生了很大的改變,再加上人口老齡化以及荷爾蒙不當(dāng)使用等原因,中國男性的前列腺癌發(fā)病率顯著上升,前景不容樂觀,越來越引起人們的重視。目前,臨床實(shí)踐中前列腺癌的治療方法主要有：手術(shù)療法、放射療法、激素療法以及化學(xué)藥物療法。手術(shù)治療、放療和激素治療能起到一定效果,然而一般情況下,盡管采取了以上措施進(jìn)行了積極治療,前列腺癌還是會(huì)繼續(xù)發(fā)展、惡化,最終發(fā)展成為雄激素非依賴性的前列腺癌(AIPC)。也就是說會(huì)導(dǎo)致上述包括激素治療在內(nèi)的治療手段的效果不理想,這時(shí),必須采用化學(xué)藥物治療(即化療)。值得注意的是,在化療藥物中,針對(duì)微管發(fā)揮作用的抗腫瘤藥物(如多西紫杉醇、卡巴他賽)在前列腺癌治療中發(fā)揮了重要作用。其中多西紫杉醇是目前治療前列腺癌標(biāo)準(zhǔn)的一線化療藥物。我們利用本實(shí)驗(yàn)室已有的合成小分子化合物庫進(jìn)行篩選,從中篩選到一個(gè)名為LG308的小分子化合物。在體外細(xì)胞實(shí)驗(yàn)中,該化合物能明顯地抑制雄激素依賴性和非依賴性的前列腺癌細(xì)胞的增殖和轉(zhuǎn)移并能明顯的將癌細(xì)胞的細(xì)胞周期進(jìn)程阻滯于G2/M期,進(jìn)而引起細(xì)胞的凋亡、死亡。進(jìn)一步研究發(fā)現(xiàn)LG308對(duì)前列腺癌細(xì)胞微管的聚合有抑制作用。為了進(jìn)一步證明LG308對(duì)于前列腺癌的抑制效果,我們接下來在動(dòng)物水平上,通過小鼠皮下荷瘤實(shí)驗(yàn)和前列腺癌原位生長、轉(zhuǎn)移實(shí)驗(yàn)進(jìn)一步檢測(cè)了小分子化合物L(fēng)G308抑制雄激素非依賴性的前列腺癌(AIPC)的作用效果。結(jié)果表明,LG308在動(dòng)物體內(nèi)水平同樣能發(fā)揮抑制前列腺癌生長、轉(zhuǎn)移的作用。綜上所述,小分子化合物L(fēng)G308通過抑制前列腺癌細(xì)胞的微管聚合作用達(dá)到在體內(nèi)和體外水平抑制前列腺癌生長轉(zhuǎn)移的效果。本研究發(fā)現(xiàn)了一種新的抗前列腺癌的潛在藥物,并為靶向微管治療前列腺癌的藥物開發(fā)提供了參考。
[Abstract]:Prostate cancer (PCA) is a malignant tumor that poses a great threat to men's health in genitourinary diseases. In the United States, men have the first new incidence of prostate cancer and the second leading cause of death in men. In China, living standards have been rising in recent years as society has developed. The changes in diet and the aging of the population and inappropriate use of hormones, the incidence of prostate cancer in China has increased significantly, the prospects are not optimistic, more and more attention. At present, the treatment of prostate cancer in clinical practice mainly includes surgical therapy, radiotherapy, hormone therapy and chemotherapeutic therapy. Surgery, radiotherapy and hormone therapy can have some effect, but in general, despite the above measures, prostate cancer will continue to develop and worsen. It eventually developed into androgen-independent prostate cancer (AIPC). In other words, these treatments, including hormone therapy, do not work well, and chemotherapeutic therapy (chemotherapy) must be used. Notably, microtubule-specific antitumor drugs (such as docetaxel, carbatin) play an important role in the treatment of prostate cancer in chemotherapeutic drugs. Among them, docetaxel is the standard first-line chemotherapeutic drug for prostate cancer. We selected a small molecular compound named LG308 from the synthetic small molecular compound library. In vitro, the compound can inhibit the proliferation and metastasis of androgen-dependent and non-dependent prostate cancer cells and block the cell cycle progression of cancer cells to G _ 2 / M phase, which leads to apoptosis. Pass away. Further studies have shown that LG308 inhibits the microtubule polymerization of prostate cancer cells. To further demonstrate the inhibitory effect of LG308 on prostate cancer, we then tested subcutaneous tumor implantation in mice and in situ growth of prostate cancer at the animal level. The effect of small molecular compound LG308 on androgen-independent prostate cancer (AIPC) was further examined by metastasis assay. The results showed that LG308 could also inhibit the growth and metastasis of prostate cancer. In conclusion, small molecular compound LG308 inhibits prostate cancer growth and metastasis in vivo and in vitro by inhibiting the microtubule polymerization of prostate cancer cells. In this study, a new potential drug against prostate cancer has been found, which provides a reference for the development of microtubule targeted drug for prostate cancer.
【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.25

【相似文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 秦敏;小分子化合物L(fēng)G308抑制前列腺癌生長和轉(zhuǎn)移的研究[D];華東師范大學(xué);2014年

，

本文編號(hào)：2051077