硫酸右旋糖酐通過影響Hif-1α、VEGF的表達(dá)抑制人胃癌細(xì)胞腹腔種植轉(zhuǎn)移的研究
本文關(guān)鍵詞:硫酸右旋糖酐通過影響Hif-1α、VEGF的表達(dá)抑制人胃癌細(xì)胞腹腔種植轉(zhuǎn)移的研究 出處:《寧夏醫(yī)科大學(xué)》2015年碩士論文 論文類型:學(xué)位論文
更多相關(guān)文章: DS 胃癌 Hif-1α VEGF MVD值 腹腔種植轉(zhuǎn)移
【摘要】:目的:探討硫酸右旋糖酐(dextran sulfate,DS)對缺氧誘導(dǎo)因子(Hif-1α)、血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)、微血管密度(MVD)的影響,觀察腹腔內(nèi)瘤結(jié)節(jié)種植情況,進(jìn)而研究DS對人胃癌細(xì)胞腹腔種植的抑制作用及其機(jī)制。方法:將72只裸鼠分為實(shí)驗(yàn)組與對照組,實(shí)驗(yàn)組40只腹腔注射濃度為1×107/m L的BGC-823人胃癌細(xì)胞0.2 m L,24h后腹腔注射0.3%DS1m L;對照組32只于注射相同濃度細(xì)胞0.2 m L 24h后,腹腔注射生理鹽水1m L。分別于1、3、7、14d時頸椎脫位法將其處死,剖腹觀察腹腔內(nèi)瘤結(jié)節(jié)的轉(zhuǎn)移情況,應(yīng)用免疫組化法檢測Hif-1α、VEGF、CD34的表達(dá),RT-PCR及Western-blot檢測Hif-1α、VEGF m RNA及蛋白的表達(dá)。結(jié)果:1.人胃癌細(xì)胞種植后1天對照組與實(shí)驗(yàn)組均未觀察到腫瘤結(jié)節(jié),隨著時間的推移,兩組瘤結(jié)節(jié)數(shù)均增多,對照組增加的幅度明顯高于實(shí)驗(yàn)組,對照組與實(shí)驗(yàn)組之間結(jié)節(jié)個數(shù)有顯著差異(P0.001)。2.免疫組化結(jié)果顯示:1天時兩組之間Hif-1α的表達(dá)無差異(P0.05),3、7、14天時兩組Hif-1α的表達(dá)均增加且有明顯差異(P0.01);對照組與實(shí)驗(yàn)組VEGF的表達(dá)均增加,兩組之間的表達(dá)有明顯差異(P0.001),實(shí)驗(yàn)組明顯低于對照組;早期隨著時間的推移MVD值明顯增高,但在后期,MVD值反而下降,總體來看,對照組與實(shí)驗(yàn)組之間在不同時間點(diǎn)上MVD值有顯著差異(P0.01),實(shí)驗(yàn)組的MVD值明顯低于對照組。3.RT-PCR結(jié)果顯示:隨著時間的推移,對照組與實(shí)驗(yàn)組Hif-1αm RNA、VEGF m RNA的表達(dá)均增加,兩組之間的表達(dá)均有明顯差異(P0.001),實(shí)驗(yàn)組明顯低于對照組。4.western-blot結(jié)果顯示:人胃癌細(xì)胞種植后1天對照組與實(shí)驗(yàn)組均未檢測到Hif-1α及VEGF的表達(dá),隨著時間的推移表達(dá)增加,Hif-1α及VEGF的表達(dá)均在兩組之間均有明顯差異(P0.001),對照組明顯高于實(shí)驗(yàn)組。5.隨著時間的推移,對照組和實(shí)驗(yàn)組Hif-1α、VEGF的表達(dá)均增加,且兩者之間的表達(dá)呈正相關(guān)。結(jié)論:1.DS可以抑制人胃癌細(xì)胞在腹腔內(nèi)的種植轉(zhuǎn)移。2.隨著人胃癌細(xì)胞種植后時間的推移,DS可以下調(diào)Hif-1α、VEGF的表達(dá)及MVD值。3.大網(wǎng)膜腫瘤組織內(nèi),Hif-1α與VEGF、VEGF及MVD值呈正相關(guān)。4.DS可能是通過下調(diào)Hif-1α、VEGF的表達(dá),并影響MVD值從而抑制人胃癌細(xì)胞的腹腔種植轉(zhuǎn)移。
[Abstract]:Objective: to investigate the effect of dextran sulfate1 DS on hypoxia inducible factor (HIF-1 偽). Effects of vascular endothelial growth factor (VEGF) on vascular endothelial growth factor (VEGF) and microvessel density (MVD). To investigate the inhibitory effect of DS on intraperitoneal implantation of gastric cancer cells and its mechanism. Methods: 72 nude mice were divided into experimental group and control group. In the experimental group, 40 BGC-823 cells with concentration of 1 脳 10 7 / mL were injected intraperitoneally with 0.3 DS 1m L for 24 h. 32 rats in the control group were killed by cervical dislocation at the time of 14 days after the same concentration of 0.2 mL cells were injected intraperitoneally with normal saline (1m L). The metastasis of tumor nodules in abdominal cavity was observed by laparotomy, and the expression of Hif-1 偽 VEGF CD34 was detected by immunohistochemical method. Hif-1 偽 was detected by RT-PCR and Western-blot. Expression of VEGF m RNA and protein. Results 1 day after implantation of human gastric cancer cells, no tumor nodules were observed in both the control group and the experimental group, and the number of tumor nodules increased in both groups with the passage of time. The increase in the control group was significantly higher than that in the experimental group. There was significant difference in the number of nodules between the control group and the experimental group. The immunohistochemical results showed that there was no difference in the expression of Hif-1 偽 between the two groups on day 1. On the 14th day, the expression of Hif-1 偽 in the two groups increased and there was significant difference between the two groups (P 0.01). The expression of VEGF in the control group and the experimental group was increased, and the expression of P0.001 was significantly different between the two groups, and the expression of VEGF in the experimental group was significantly lower than that in the control group. In the early stage, the MVD value increased obviously with the passage of time, but decreased in the later stage. In general, there was a significant difference in MVD between the control group and the experimental group at different time points (P0.01). The MVD value of the experimental group was significantly lower than that of the control group. 3. The results of RT-PCR showed that the Hif-1 偽 m RNA of the control group and the experimental group was higher than that of the control group. The expression of VEGF m RNA increased, and there was significant difference between the two groups (P 0.001). The results of Western blot showed that the expression of Hif-1 偽 and VEGF was not detected in the control group and the experimental group 1 day after implantation. The expression of Hif-1 偽 and VEGF increased with the passage of time in both groups. The expression of Hif-1 偽 and VEGF in the control group was significantly higher than that in the experimental group. The expression of Hif-1 偽 -VEGF was increased in both control group and experimental group. Conclusion: 1. DS can inhibit the implantation metastasis of human gastric cancer cells in abdominal cavity. 2. With the passage of time after implantation of human gastric cancer cells, DS can down-regulate Hif-1 偽. VEGF expression and MVD value. 3. Hif-1 偽 was positively correlated with VEGF and MVD in omental tumors. 4. DS may be by down-regulating Hif-1 偽. The expression of VEGF and the effect of MVD on the metastasis of human gastric cancer cells.
【學(xué)位授予單位】:寧夏醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2015
【分類號】:R735.2
【共引文獻(xiàn)】
相關(guān)期刊論文 前3條
1 何清;焦?jié)嵢?魏旭清;趙雅潔;吳方;;胃腸癌患者外周血腫瘤標(biāo)志物檢測的臨床研究[J];臨床消化病雜志;2010年02期
2 趙雪艷;王娟;榮小偉;徐遠(yuǎn)義;;DS對胃癌細(xì)胞整合素β1表達(dá)及腹腔種植轉(zhuǎn)移的影響[J];臨床與實(shí)驗(yàn)病理學(xué)雜志;2013年04期
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