癌细胞自噬水平调节结肠癌细胞化疗耐药性的分子机制  

Molecular mechanism of autophagy level in cancer cells regulating of chemoresistance in colon cancer cells

作　　者：朱国强[1] ZHU Guo-qiang(Department of General Surgery,First Affiliated Hospital of Nanyang Medical College,Nanyang 473000,China)

机构地区：[1]南阳医学高等专科学校第一附属医院普外科,河南南阳473000

出　　处：《中国现代普通外科进展》2020年第11期851-854,共4页Chinese Journal of Current Advances in General Surgery

摘　　要：目的:从癌细胞自噬水平研究其对结肠癌细胞化疗耐药性的分子机制。方法:将人SW480结肠癌细胞作为对照组,将添加5-氟尿嘧啶(5-FU)培养的人SW480结肠癌细胞模拟临床化疗作为实验组。通过透射电子显微镜、蛋白质免疫印迹、流式细胞术和定量实时聚合酶链式反应(PCR)检测两组细胞自噬泡数量,B细胞淋巴细胞瘤/白血病-2(Bcl-2)相关X蛋白(Bax)、含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3)、Bcl-2、微管相关蛋白I轻链3-I(LC3-I)和微管相关蛋白I轻链3-II(LC3-II)蛋白表达,细胞凋亡率,Akt、Erk1/2及CD44v6的基因相对表达水平。结果:与对照组相比,实验组自噬体的数量增加,Bax和Caspase-3蛋白表达增高,Bcl-2蛋白表达降低,LC3-I/LC3-II蛋白表达比例增高(均P<0.05)。与对照组比较,实验组细胞凋亡率降低(P<0.05)。与对照组相比,实验组细胞中p-Akt和p-Erk1/2及CD44v6基因表达增高(均P<0.05)。结论:CD44v6可能通过激活PI3K-Akt和MAPK-Ras-Erk1/2通路促进癌细胞自噬,增加结肠癌细胞对化疗的耐药性。Objective: To study the molecular mechanism of chemoresistance to colon cancer cells from the level of autophagy in cancer cells. Methods: Human SW480 colon cancer cells were used as the control group, and human SW480 colon cancer simulated clinical chemotherapy supplemented with 5-fluorouracil(5-FU) was used as the experimental group. The number of autophagic vesicles, Bcl-2 related X protein(Bax), Aspartate proteolytic enzyme 3(Caspase-3), B cell lymphoma/leukemia-2(Bcl-2), microtubule-associated protein I light chain 3-I(LC3-I) and microtubule-associated protein I light chain 3-II(LC3-II) protein expression, apoptosis rate, relative expression levels of Akt, Erk1/2 and CD44 v6 genes in 2 groups were detected by transmission electron microscopy, Western blotting, flow cytometry and quantitative real-time polymerase chain reaction(PCR). Results: Compared with the control group, the number of autophagosomes had increased,Bax and caspase-3 protein expression had increased, Bcl-2 protein expression had decreased,LC3-I/LC3-II protein expression ratio had increased in the experimental group(P<0.05). Compared with the control group, the apoptosis rate of the experimental group had decreased(P<0.05). Compared with the control group, the p-Akt and p-Erk1/2 and CD44 v6 gene expression had increased in the experimental group cells(both P<0.05). Conclusion: CD44 v6 may promote the autophagy of cancer cells by activating PI3 K-Akt and MAPK-Ras-Erk1/2 pathways, and increase the resistance of colon cancer cells to chemotherapy.

关 键 词：结肠癌 自噬 化疗 耐药性 

分 类 号：R737.31[医药卫生—肿瘤]