【摘要】：目的:探討宮頸癌細(xì)胞來(lái)源白細(xì)胞介素-27(IL-27)是否調(diào)節(jié)血管內(nèi)皮細(xì)胞的生物學(xué)行為,并參與血管生成。方法:分別通過免疫組化,ELISA和流式細(xì)胞術(shù)分析IL-27在宮頸癌組織和宮頸細(xì)胞系(HeLa和CaSki細(xì)胞)中的表達(dá)情況。研究IL-27過表達(dá)宮頸癌細(xì)胞系后對(duì)人臍靜脈內(nèi)皮細(xì)胞(HUVECs)增殖和凋亡相關(guān)分子的作用,以及HUVECs體外血管形成情況。最后,進(jìn)行體內(nèi)實(shí)驗(yàn)以進(jìn)一步確認(rèn)。結(jié)果:相對(duì)于宮頸炎組織,宮頸癌組織高度表達(dá)IL-27。HeLa和CaSki細(xì)胞系分泌IL-27,HUVECs表達(dá)低水平的IL-27受體(IL-27R:WSX-1和gp130)。然而,宮頸細(xì)胞系和HUVECs共培養(yǎng)導(dǎo)致HUVECs的IL-27R和IL-27+HeLa細(xì)胞百分比顯著升高,但是IL-27+CasKi細(xì)胞百分比降低。過表達(dá)IL-27的HeLa細(xì)胞下調(diào)HUVECs的Ki-67和Bcl-2表達(dá)水平,上調(diào)Fas表達(dá)水平。此外,過表達(dá)IL-27的HeLa細(xì)胞和CasKi細(xì)胞于對(duì)照組相比,減少IL-8的分泌,并且通過減少IL-8水平,進(jìn)一步抑制血管內(nèi)皮細(xì)胞血管形成。在C57/BL6小鼠的皮下建腫瘤模型中,當(dāng)接種慢病毒IL-27轉(zhuǎn)染的TC-1細(xì)胞時(shí),腫瘤中血管密度和腫瘤體積都減少。結(jié)論:宮頸癌細(xì)胞分泌IL-27以旁分泌方式的限制血管生成并抑制在宮頸癌的生長(zhǎng)。
[Abstract]:Aim: to investigate whether interleukin-27 (IL-27), derived from cervical cancer cells, regulates the biological behavior of vascular endothelial cells and participates in angiogenesis. Methods: the expression of IL-27 in cervical carcinoma tissues and cervical cell lines (HeLa and CaSki cells) was analyzed by immunohistochemistry Elisa and flow cytometry respectively. To study the effect of IL-27 overexpression on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the angiogenesis of HUVECs in vitro. Finally, in vivo experiments were carried out for further confirmation. Results: compared with cervicitis tissues, cervical cancer tissue highly expressed IL-27. HeLa and CaSki cells secreted IL-27 and HUVECs with low expression level of IL-27 receptor (IL-27 R: WSX-1 and gp130). However the percentage of IL-27R and IL-27 HeLa cells in HUVECs was significantly increased but the percentage of IL-27 CasKi cells was decreased. Overexpression of IL-27 in HeLa cells down-regulated the expression of Ki-67 and Bcl-2 and up-regulated FAS expression in HUVECs. In addition, the overexpression of IL-27 in HeLa cells and CasKi cells decreased the secretion of IL-8, and further inhibited the angiogenesis of vascular endothelial cells by reducing the level of IL-8. In the subcutaneous tumor model of C57 / BL6 mice, the vascular density and tumor volume in the tumor were decreased when the TC-1 cells transfected with lentivirus IL-27 were inoculated. Conclusion: IL-27 secreted by cervical cancer cells inhibits angiogenesis and inhibits the growth of cervical cancer in a paracrine manner.
【學(xué)位授予單位】：江南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.33

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