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二甲双胍通过抑制糖代谢部分逆转非小细胞肺癌对卡铂的耐药性。

Metformin partially reverses the carboplatin-resistance in NSCLC by inhibiting glucose metabolism.

作者信息

Liu Yong, He Chunxi, Huang Xianping

机构信息

Department of Cardiothoracic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.

出版信息

Oncotarget. 2017 Sep 6;8(43):75206-75216. doi: 10.18632/oncotarget.20663. eCollection 2017 Sep 26.

DOI:10.18632/oncotarget.20663
PMID:29088858
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5650413/
Abstract

Platinum-based chemotherapeutic drugs are irreplaceable for the treatment of advanced non-small cell lung cancer (NSCLC). However, acquired drug resistance has become a major obstacle for the clinical application of chemotherapy on NSCLC. In the present study, we established carboplatin-resistant NSCLC models on A549 and PC9 cell lines, which were named A549/R and PC9/R. Besides the low sensitivity of A549/R and PC9/R to carboplatin treatment, they exhibited higher metabolism rate of glucose compared to their parental A549 and PC9 cells, respectively. Mechanically, we confirmed that overexpression of PKM2 in A549/R and PC9/R was responsible for the high glucose metabolism and carboplatin resistance. Metformin, an antidiabetic drug, was observed to increase the sensitivity of carboplatin-resistant NSCLC cells to carboplatin treatment and . Mechanically, metformin decreased expression of PKM2 and subsequently inhibited the glucose uptake, lactate generation and ATP production in A549/R and PC9/R. Therefore, metformin promoted carboplatin-induced apoptosis through the mitochondria pathway. In addition, we demonstrated that metformin treatment also impaired the cross-resistance of A549/R and PC9/R to cisplatin, etoposide and 5-fluorouracil.

摘要

铂类化疗药物在晚期非小细胞肺癌（NSCLC）的治疗中具有不可替代的作用。然而，获得性耐药已成为化疗在NSCLC临床应用中的主要障碍。在本研究中，我们在A549和PC9细胞系上建立了卡铂耐药的NSCLC模型，分别命名为A549/R和PC9/R。除了A549/R和PC9/R对卡铂治疗的低敏感性外，它们与亲本A549和PC9细胞相比，分别表现出更高的葡萄糖代谢率。从机制上讲，我们证实A549/R和PC9/R中PKM2的过表达是高糖代谢和卡铂耐药的原因。观察到抗糖尿病药物二甲双胍可增加卡铂耐药NSCLC细胞对卡铂治疗的敏感性。从机制上讲，二甲双胍降低了PKM2的表达，随后抑制了A549/R和PC9/R中的葡萄糖摄取、乳酸生成和ATP产生。因此，二甲双胍通过线粒体途径促进卡铂诱导的细胞凋亡。此外，我们证明二甲双胍治疗还削弱了A549/R和PC9/R对顺铂、依托泊苷和5-氟尿嘧啶的交叉耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/c1ad5901209c/oncotarget-08-75206-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/57ff17eee081/oncotarget-08-75206-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/af04d99df606/oncotarget-08-75206-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/445aee510e30/oncotarget-08-75206-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/0087b5af59b8/oncotarget-08-75206-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/84f9f69806c5/oncotarget-08-75206-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/78e7b85d143d/oncotarget-08-75206-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/c1ad5901209c/oncotarget-08-75206-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/57ff17eee081/oncotarget-08-75206-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/af04d99df606/oncotarget-08-75206-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/445aee510e30/oncotarget-08-75206-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/0087b5af59b8/oncotarget-08-75206-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/84f9f69806c5/oncotarget-08-75206-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/78e7b85d143d/oncotarget-08-75206-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3213/5650413/c1ad5901209c/oncotarget-08-75206-g007.jpg

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1
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2
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Oncotarget. 2017 Jan 31;8(5):8622-8632. doi: 10.18632/oncotarget.14373.
3
Metformin Induces Growth Inhibition and Cell Cycle Arrest by Upregulating MicroRNA34a in Renal Cancer Cells.
去甲二氢愈创木酸对非小细胞肺癌（NSCLC）细胞系增殖、能量代谢和化疗增敏的影响。
Int J Mol Sci. 2024 Oct 29;25(21):11601. doi: 10.3390/ijms252111601.
4
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5
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Int J Mol Sci. 2022 Dec 21;24(1):97. doi: 10.3390/ijms24010097.
6
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7
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