葡萄糖调节蛋白78通过线粒体凋亡通路调节前列腺癌细胞增殖-现代医学

葡萄糖调节蛋白78通过线粒体凋亡通路调节前列腺癌细胞增殖

作者：龚娟卢童

单位：湖北省天门市第一人民医院泌尿外科, 湖北天门 431700

分类号：R737.25

出版年·卷·期（页码）：2018·46·第二期（121-125）

摘要：

目的：探讨葡萄糖调节蛋白78（GRP78）对前列腺癌细胞增殖的调控作用及机制。方法：采用免疫组织化学染色检测60例前列腺癌和40例40例良性前列腺增生组织GRP78表达；利用反义核苷酸技术下调PC-3细胞GRP78表达，CCK-8检测细胞增殖能力，流式细胞术检测细胞凋亡率，Western blot检测线粒体凋亡通路相关蛋白的表达。结果：前列腺增生组织GRP78蛋白阳性率（86.7%，52/60）明显高于前列腺增生组织（35.0%，14/60）（χ²=28.550，P<0.000 1）。转染组在24 h、48 h、72 h后增殖能力明显低于阴性对照组和空白对照组（P<0.05），阴性对照组和空白对照组细胞增殖能力比较差异无统计学意义（P>0.05）。与阴性对照组和空白对照组比较，转染组细胞凋亡率明显增加（P<0.05），阴性对照组和空白对照组细胞凋亡率比较差异无统计学意义（P>0.05）。与阴性对照组和空白对照组比较，转染组细胞Caspase-9、Bax蛋白表达明显增加，Bcl-2蛋白表达明显减少（P<0.05），阴性对照组和空白对照组Caspase-9、Bcl-2、Bax蛋白表达比较差异无统计学意义（P>0.05）。结论：下调GRP78表达可以抑制前列腺癌细胞的增殖和促进细胞凋亡，GRP78可能通过线粒体凋亡通路调控前列腺癌细胞的增殖。

Objective: To explore the effect of glucose regulated protein 78(GRP78) on prostatic carcinoma cell growth and its mechanism. Methods: The expression of GRP78 in sixty prostatic carcinoma patients and forty benign prostatic hyperplasia patients tissues was measured by immunohistochemistryassay, and the expression of GRP78 was down-regulated by antisense nucleotide technology, the ability of cell proliferation was measured by CCK-8 assay, the cell apoptosis was measured by flow cytometry, the relative protein expression of mitochondrial apoptotic pathway was performed by Western blot. Results: The positive rate of GRP78 protein in the prostatic carcinoma group(86.7%, 52/60) was significantly lower than that in the BPH group(35.0%, 14/60)(χ²=28.550, P<0.0001). After 24 h, 48 h, 72 h of transfection, the cell proliferation ability in the transfection group was significantly lower than that in the negative group and the blank control group(P<0.05), while there was no significant difference of proliferation between the negative group and the blank control group(P>0.05). Compared with the negative group and the blank control group, the apoptosis rate in the transfection group was remarkably increased, while there was no significant difference in the negative group and the blank control group(P>0.05).Compared with negative group and blank control group, the expression of Caspase-9, Bax protein in the transfection group was remarkably increased, Bcl-2 was obviously decreased, there was no significant difference in the negative group and blank control group(P>0.05). Conclusion: Down-regulating the expression of GRP78 in the prostatic carcinoma cell can obviously inhibit the cell proliferation and promote cell apoptosis, and mitochondrial apoptotic pathway may involve the GRP78-mediated prostatic carcinoma cell proliferation.

参考文献：

[1] LAN J,XU W,WAN Q,et al.Colorimetric determination of sarcosine in urine samples of prostatic carcinoma by mimic enzyme palladium nanoparticles[J].Anal Chim Acta,2014,825:63-68.
[2] ZHANG H,LV M,JIA J,et al.Expression of the 78 kD glucose-regulated protein is induced by endoplasmic reticulum stress in the development of hepatopulmonary syndrome[J].Gene,2014,537(1):115-119.
[3] KILINC V,BEDIR A,OKUYUCU A,et al.Do iron chelators increase the antiproliferative effect of trichostatin A through a glucose-regulated protein 78 mediated mechanism?[J].Tumour Biol,2014,35(6):5945-5951.
[4] TAKATO H,SHIMIDZU M,ASHIZAWA Y,et al.An acyl-CoA-binding protein from grape that is induced through ER stress confers morphological changes and disease resistance in Arabidopsis[J].J Plant Physiol,2013,170(6):591-600.
[5] 魏华,景红,吴江,等.胃癌中葡萄糖调节蛋白78和葡萄糖调节蛋白94表达的临床意义及与预后的相关性[J].首都医科大学学报,2014,35(4):501-506.
[6] 王斌,刘景丰,金杰钿,等.热休克蛋白70和葡萄糖调节蛋白78在肝细胞癌中的表达及其临床意义[J].中华实验外科杂志,2014,31(10):2115-2118.
[7] 牛哲禹,刘乔飞,王梦一,等.葡萄糖调节蛋白78在小鼠胰腺癌发生演进过程中的表达变化[J].中国医学科学院学报,2015,37(3):259-263.
[8] BHATTACHARJEE R,DEVI A,MISHRA S.Molecular docking and molecular dynamics studies reveal structural basis of inhibition and selectivity of inhibitors EGCG and OSU-03012 toward glucose regulated protein-78(GRP78) overexpressed in glioblastoma[J].J Mol Model,2015,21(10):272.
[9] 王进举,张春燕,肖斌,等.GRP78在肝癌细胞抵抗棕榈酸诱导凋亡中的作用[J].中国老年学杂志,2016,36(9):2056-2059.
[10] LU T,YANG W,WANG Z,et al.Knockdown of glucose-regulated protein 78/binding immunoglobulin heavy chain protein expression by asymmetric small interfering RNA induces apoptosis in prostate cancer cells and attenuates migratory capability[J].Mol Med Rep,2015,11(1):249-256.
[11] 邵芙蓉,王靓,储晓琴,等.氯尼达明诱导乳腺癌MCF-7细胞凋亡的作用及机制[J].南方医科大学学报,2015,(6):883-887.
[12] 周静,韦红梅,戎嵘,等.大豆异黄酮对人乳腺癌MCF-7细胞侵袭转移能力的影响及其与PPAR γ的关系研究[J].营养学报,2012,34(1):58-63.
[13] DAS S,MOHAPATRA A,SAHOO P K.Expression analysis of heat shock protein genes during Aeromonas hydrophila infection in rohu,Labeo rohita,with special reference to molecular characterization of Grp78[J].Cell Stress Chaperones,2015,20(1):73-84.
[14] TIAN S,CHANG W,DU H,et al.The interplay between GRP78 expression and Akt activation in human colon cancer cells under celecoxib treatment[J].Anticancer Drugs,2015,26(9):964-973.
[15] PINKAEW D,CHANGTAM C,TOCHARUS C,et al.Di-O-demethylcurcumin protects SK-N-SH cells against mitochondrial and endoplasmic reticulum-mediated apoptotic cell death induced by A beta(25-35)[J].Neurochem Int,2015,80(1):110-119.
[16] 郑天胜.线粒体凋亡通路的研究进展[J].医学综述,2013,19(18):3282-3285.

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