Autophagy activation contributes to glutathione transferase Mu 1-mediated chemoresistance in hepatocellular carcinoma.
Autophagy activation contributes to glutathione transferase Mu 1-mediated chemoresistance in hepatocellular carcinoma.
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自噬激活有助于谷胱甘肽转移酶 Mu 1 介导的肝细胞癌化疗耐药。
DOI：
10.3892/ol.2018.8667
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发表时间：
2018-07
期刊：
影响因子：
2.9
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Fu XT;Song K;Zhou J;Shi YH;Liu WR;Tian MX;Jin L;Shi GM;Gao Q;Ding ZB;Fan J
谷胱甘肽转移酶Mu1(GSTM1)通过水解癌化疗药物或激活抗细胞凋亡途径诱导肿瘤耐药。然而，GSTM1在肝细胞癌中诱导化疗耐药的机制尚不清楚。在本研究中，我们检测了GSTM1在三个肝癌细胞系中的表达。化疗药物选用奥沙利铂和索拉非尼。小干扰RNA用于降低GSTM1的表达。用四甲基偶氮唑盐比色法和膜联蛋白V/碘化丙啶比色法检测细胞死亡。通过绿色荧光蛋白轻链3重分布和分析自噬相关基因5在MHCC97-H和Huh-7细胞中的表达来评价自噬的激活。随着肝癌细胞系转移潜能的增加，GSTM1的表达逐渐增强。GSTM1基因敲除MHCC97-H和Huh-7细胞后，奥沙利铂和索拉非尼诱导的细胞死亡明显增加。抑制GSTM1的表达可显著抑制自噬的激活。本研究结果提示，GSTM1可能通过激活自噬来保护肝癌细胞免受奥沙利铂治疗的影响。本研究为研究肝癌的耐药性提供了一个新的视角。
Glutathione transferase Mu 1 (GSTM1) induces cancer drug resistance by hydrolyzing cancer chemotherapeutics or activating the anti-apoptosis pathway. However, the chemoresistance-inducing mechanism of GSTM1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of GSTM1 was examined in three HCC cell lines. Oxaliplatin and sorafenib were selected as chemotherapeutic agents. Small interfering RNA was used to decrease GSTM1 expression. Cell death was measured using MTT and annexin V/propidium iodide assays. Activation of autophagy was evaluated by green fluorescent protein-light chain 3 redistribution and analysis of autophagy-related 5 expression in MHCC97-H and Huh-7 cells. A stepwise increase in GSTM1 expression with increasing metastatic potential of HCC cell lines was revealed. Cell death induced by oxaliplatin and sorafenib was significantly increased following GSTM1-knockdown in MHCC97-H and Huh-7 cells. Activation of autophagy was significantly inhibited by silencing GSTM1 expression. The results of the present study suggest that GSTM1 may protect HCC cells against the effect of oxaliplatin treatment through activating autophagy. The present study provides a novel perspective on HCC drug-resistance.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
影响因子：
3.7
作者：
King FW;Fong S;Griffin C;Shoemaker M;Staub R;Zhang YL;Cohen I;Shtivelman E
通讯作者：
Shtivelman E
DOI：
10.1055/s-0033-1343232
发表时间：
2013-07-01
期刊：
Deutsche medizinische Wochenschrift (1946)
影响因子：
--
作者：
Gobel, T;Blondin, D;Erhardt, A
通讯作者：
Erhardt, A
影响因子：
25.7
作者：
Chen X;Lingala S;Khoobyari S;Nolta J;Zern MA;Wu J
通讯作者：
Wu J
影响因子：
11.2
作者：
Wilhelm, SM;Carter, C;Trail, PA
通讯作者：
Trail, PA