己糖激酶2的二聚作用以及与电压依赖性阴离子通道的相互作用促进了吉西他滨在胰腺癌中诱导的对细胞凋亡的抗性。,Cancer Medicine

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己糖激酶2的二聚作用以及与电压依赖性阴离子通道的相互作用促进了吉西他滨在胰腺癌中诱导的对细胞凋亡的抗性。
Cancer Medicine ( IF 2.9 ) Pub Date : 2019-08-19 , DOI: 10.1002/cam4.2463
Kun Fan _{1,

2,

3,

4} , Zhiyao Fan _{1,

2,

3,

4} , He Cheng _{1,

2,

3,

4} , Qiuyi Huang _{1,

2,

3,

4} , Chao Yang _{1,

2,

3,

4} , Kaizhou Jin _{1,

2,

3,

4} , Guopei Luo _{1,

2,

3,

4} , Xianjun Yu _{1,

2,

3,

4} , Chen Liu _{1,

2,

3,

4}

Affiliation

吉西他滨（GEM）是胰腺癌的标准化疗药物。由于广泛的耐药性，其作用是有限的。因此，迫切需要揭示其潜在机制。糖酵解是肿瘤异常代谢的最显着特征，它在肿瘤耐药性中起着至关重要的作用。己糖激酶2（HK2）作为调节糖酵解第一步反应的关键酶，在许多类型的肿瘤中均过表达。在这项研究中调查了HK2抵抗GEM治疗的推定作用。我们发现HK2在胰腺癌中过表达，并与不良预后相关。HK2组合式降低胰腺癌细胞的增殖，迁移活力，并促进体外细胞凋亡。HK2在胰腺癌中的高表达显示出GEM耐药性。HK2敲除增加了胰腺癌细胞对GEM的敏感性，与体内对照相比，GEM治疗还进一步降低了带有HK2敲除的异种移植瘤的生长。耐GEM的胰腺癌显示HK2二聚体增加，而不是HK2 mRNA或蛋白质增加。我们的研究表明，GEM衍生的ROS促进了HK2二聚化并结合了电压依赖性阴离子通道，从而导致了对GEM的抗性。同时，我们的研究为胰腺癌的GEM耐药性树立了新视野。我们的研究表明，GEM衍生的ROS促进了HK2二聚化并结合了电压依赖性阴离子通道，从而导致了对GEM的抗性。同时，我们的研究为胰腺癌的GEM耐药性树立了新视野。我们的研究表明，GEM衍生的ROS促进了HK2二聚化并结合了电压依赖性阴离子通道，从而导致了对GEM的抗性。同时，我们的研究为胰腺癌的GEM耐药性树立了新视野。

"点击查看英文标题和摘要"

Hexokinase 2 dimerization and interaction with voltage-dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer.

Gemcitabine (GEM) is the standard chemotherapy drug for pancreatic cancer. Because of widespread drug resistance, the effect is limited. Therefore, it is urgent to reveal the underlying mechanism. Glycolysis is the most remarkable character of tumor aberrant metabolism, which plays vital roles on tumor drug resistance. Hexokinase 2 (HK2), as the key enzyme regulating the first‐step reaction of glycolysis, is overexpressed in many kinds of tumors. The putative role of HK2 resisting GEM therapy was investigated in this study. We found that HK2 was overexpressed in pancreatic cancer and associated with poor prognosis. HK2 knockdown decreased pancreatic cancer cell proliferation, migration viability, and promoted cell apoptosis in vitro. HK2 high expression in pancreatic cancer showed GEM resistance. HK2 knockdown increased the sensitivity of pancreatic cancer cell to GEM, the growth of xenograft tumor with HK2 knockdown was also further decreased with the GEM treatment compared with control in vivo. GEM‐resistant pancreatic cancer showed the increase of HK2 dimer rather than HK2 mRNA or protein. Our study revealed that the ROS derived from GEM promoted HK2 dimerization combining with voltage‐dependent anion channel, which resulted in the resistance to GEM. Meanwhile, our study established a new sight for GEM resistance in pancreatic cancer.

更新日期：2019-08-20

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