The effects and mechanisms of mitochondrial fission mediated by mitochondrial dynamics related protein DRP1 on glucose metabolism reprogramming in lung cancer cells <i>via</i> PI3K/Akt signaling pathway_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

LUO Yi ¹ , XIONG Xie ² ,  XU Jinsong ¹

1. Department of Respiratory Medicine, 908S1 Hospital, PLA Joint Logistic Support Force, Nanchang, Jiangxi 330000, P. R. China;
2. Department of Oncology, 908S1 Hospital, PLA Joint Logistic Support Force, Nanchang, Jiangxi 330000, P. R. China;

Corresponding author：

XU Jinsong, Email: xujinsong@126.com

Keywords：

Dynamin-related protein 1; mitochondrial fission; phosphatidylinositol-3-kinases/protein kinase B signaling pathway; lung cancer; glycolysis; proliferation; apoptosis

DOI：

10.7507/1671-6205.202408082

Video：

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Objective To investigate the effect of mitochondrial fission mediated by mitochondrial dynamics related protein 1 (DRP1) on glucose metabolism reprogramming in lung cancer cells, and the regulatory mechanism on phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt) signaling pathway. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of DRP1 in lung cancer tissue and lung cancer cells. Mitochondrial fission inhibitor (Mdivi-1) and Mdivi-1+PI3K/Akt signaling pathway activator 740Y-P were used to treat H1299 cells. Mitochondrial fission agonist (WY14643) + signal inhibitor LY294002 were used to intervene PC14 cells. The reagent kit was used to detect the glucose consumption, lactate release, and ATP production of each group of cells. 5-ethynyl-2-deoxyuridine (EdU) labeling experiment was used to detect the proliferation of cells in each group, and acridine orange/ethidium bromide (AO/EB) staining was used to detect the apoptosis of cells in each group. MitoTracker Red CMXRos was used to detect the mitochondrial morphology of each group of cells. Tetramethylrhodamine ethyl ester (TMRE) staining was used to detect the mitochondrial membrane potential of cells. Dihydroethidium (DHE) staining was used to detect the level of reactive oxygen species (ROS) in cells. Western blot was used to detect was used to detect the expression of pyruvate kinase M2 (PKM2), hexokinase 2 (HK2), phosphofructokinase-1 (PFK1), DRP1, phosphorylated DRP1 (p-DRP1), PI3K, Akt, phosphorylated PI3K (p-PI3K), and phosphorylated Ak t(p-Akt) in each group of cells. Results The mRNA expression of DRP1 was significantly increased in lung cancer tissue and lung cancer cells. Mdivi-1 promoted the development of lung cancer and exerts anticancer effects, while activating PI3K/Akt signaling could partially reverse the anticancer effects of Mdivi-1. WY14643 exerted a pro-cancer effect, and inhibiting PI3K/Akt signaling could partially reverse the pro-cancer effect of WY14643, and the differences were statistically significant (all P<0.05). Conclusion s In lung cancer, the expression of DRP1 is significantly increased, and DRP1 affects the glycolysis process and proliferation performance of lung cancer cells by regulating the activation of PI3K/Akt signaling.

1.	王燕, 徐春华, 李丽, 等. 应变弹性成像及声触诊组织成像定量技术对肺癌患者颈部淋巴结性质判定的价值. 中国呼吸与危重监护杂志, 2024, 23(6): 395-399.
2.	Zhang YF, Yuan LL, Wang ZC, et al. DHEA down-regulates mitochondrial dynamics and promotes apoptosis of lung adenocarcinoma cells through FASTKD2. J Cancer, 2024, 15(8): 2110-2122.
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4.	李琦, 黄广智, 李亚军, 等. miR-106a通过调控PI3K/PDK1/AKT蛋白通路调节胃癌细胞生物学行为的研究. 解剖学研究, 2024, 46(2): 132-138.
5.	Mohanty D, Padhee S, Priyadarshini A, et al. Elucidating the anti-cancer potential of Cinnamomum tamala essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations. Heliyon, 2024, 10(6): e28026.
6.	Cardaci TD, VanderVeen BN, Bullard BM, et al. Obesity worsens mitochondrial quality control and does not protect against skeletal muscle wasting in murine cancer cachexia. J Cachexia Sarcopenia Muscle, 2024, 15(1): 124-137.
7.	Alizadeh J, da Silva Rosa SC, Cordani M, et al. Evaluation of mitochondrial phagy (mitophagy) in human non-small adenocarcinoma tumor cells. Methods Mol Biol, 2025, 2879: 261-273.
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11.	Luo W, Chang G, Lin D, et al. 3, 3'-((3, 4, 5-trifluoropHenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) inhibit lung cancer cell proliferation and migration. PLoS One, 2024, 19(5): e0303186.
12.	方汉林, 潘华光, 陈宇, 等. MRPL21调控YAP1/TAZ通路对非小细胞肺癌A549细胞活性的影响. 医学分子生物学杂志, 2024, 21(4): 329-333.
13.	Zhou Y, Zhang Y, Xu J, et al. Schwann cell-derived exosomes promote lung cancer progression via miRNA-21-5p. Glia, 2024, 72(4): 692-707.
14.	叶磊, 方申存, 张海涛, 等. 肺癌患者免疫检查点抑制剂相关肺炎危险因素: 基于真实世界研究的Meta分析. 中国呼吸与危重监护杂志, 2023, 22(6): 408-417.
15.	第伍丹琲, 王虹, 陶红艳, 等. 鸦胆子素A通过EMT信号诱导非小细胞肺癌细胞凋亡. 中国药理学通报, 2024, 40(8): 1474-1481.
16.	冯亚婵, 张皓杰, 杜朝, 等. 青蒿素通过TIGIT/CD155信号轴调控4T1乳腺癌细胞转移与凋亡. 中国生物化学与分子生物学报, 2024, 40(1): 131-141.
17.	Ding R, Wang Y, Xu L, et al. QiDongNing induces lung cancer cell apoptosis via triggering P53/DRP1-mediated mitochondrial fission. J Cell Mol Med, 2024, 28(9): e18353.
18.	Wu Z, Xiao C, Li F, et al. Mitochondrial fusion-fission dynamics and its involvement in colorectal cancer. Mol Oncol, 2024, 18(5): 1058-1075.
19.	Ding Y, Lv Z, Cao W, et al. Phosphorylation of INF2 by AMPK promotes mitochondrial fission and oncogenic function in endometrial cancer. Cell Death Dis, 2024, 15(1): 65.
20.	Xiao J, Wang S, Chen L, et al. 25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages. Immunity, 2024, 57(5): 1087-1104.
21.	Nath S, Patra D, Nag A, et al. Sesquiterpenoid-rich Java Ginger rhizome extract prompts autophagic cell death in cervical cancer cell SiHa mainly by modulating cellular redox homeostasis. 3 Biotech. 2023, 13(1): 8.
22.	鲁丁瑜, 廖建, 吴飞, 等. ECT2通过调控PI3K/AKT信号通路对胰腺癌细胞恶性行为、糖酵解及TH细胞分化的影响. 解剖学研究, 2023, 45(4): 329-336,341.
23.	Egusquiza-Alvarez CA, Moreno-Londoño AP, Alvarado-Ortiz E, et al. Inhibition of Multifunctional Protein p32/C1QBP Promotes Cytostatic Effects in Colon Cancer Cells by Altering Mitogenic Signaling Pathways and Promoting Mitochondrial Damage. Int J Mol Sci, 2024, 25(5): 2712.

1. 王燕, 徐春华, 李丽, 等. 应变弹性成像及声触诊组织成像定量技术对肺癌患者颈部淋巴结性质判定的价值. 中国呼吸与危重监护杂志, 2024, 23(6): 395-399.
2. Zhang YF, Yuan LL, Wang ZC, et al. DHEA down-regulates mitochondrial dynamics and promotes apoptosis of lung adenocarcinoma cells through FASTKD2. J Cancer, 2024, 15(8): 2110-2122.
3. Tsutsumi K, Tippayamontri T, Hayashi M, et al. The dynamic relationship between inorganic polyphosphate and adenosine triphosphate in human non-small cell lung cancer H1299 cells. FEBS Open Bio, 2024, 4(2): 344-354.
4. 李琦, 黄广智, 李亚军, 等. miR-106a通过调控PI3K/PDK1/AKT蛋白通路调节胃癌细胞生物学行为的研究. 解剖学研究, 2024, 46(2): 132-138.
5. Mohanty D, Padhee S, Priyadarshini A, et al. Elucidating the anti-cancer potential of Cinnamomum tamala essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations. Heliyon, 2024, 10(6): e28026.
6. Cardaci TD, VanderVeen BN, Bullard BM, et al. Obesity worsens mitochondrial quality control and does not protect against skeletal muscle wasting in murine cancer cachexia. J Cachexia Sarcopenia Muscle, 2024, 15(1): 124-137.
7. Alizadeh J, da Silva Rosa SC, Cordani M, et al. Evaluation of mitochondrial phagy (mitophagy) in human non-small adenocarcinoma tumor cells. Methods Mol Biol, 2025, 2879: 261-273.
8. Yan F, Teng Y, Li X, et al. Hypoxia promotes non-small cell lung cancer cell stemness, migration, and invasion via promoting glycolysis by lactylation of SOX9. Cancer Biol Ther, 2024, 25(1): 2304161.
9. 王美晴, 白虎成, 张枢, 等. 新型KRASG12C抑制剂VT198的药效学及药动学研究. 中国新药杂志, 2024, 33(14): 1466-1471.
10. Manandhar B, Paudel KR, Clarence DD, et al. Zerumbone-incorporated liquid crystalline nanoparticles inhibit proliferation and migration of non-small-cell lung cancer in vitro. Naunyn Schmiedebergs Arch Pharmacol, 2024, 397(1): 343-356.
11. Luo W, Chang G, Lin D, et al. 3, 3'-((3, 4, 5-trifluoropHenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) inhibit lung cancer cell proliferation and migration. PLoS One, 2024, 19(5): e0303186.
12. 方汉林, 潘华光, 陈宇, 等. MRPL21调控YAP1/TAZ通路对非小细胞肺癌A549细胞活性的影响. 医学分子生物学杂志, 2024, 21(4): 329-333.
13. Zhou Y, Zhang Y, Xu J, et al. Schwann cell-derived exosomes promote lung cancer progression via miRNA-21-5p. Glia, 2024, 72(4): 692-707.
14. 叶磊, 方申存, 张海涛, 等. 肺癌患者免疫检查点抑制剂相关肺炎危险因素: 基于真实世界研究的Meta分析. 中国呼吸与危重监护杂志, 2023, 22(6): 408-417.
15. 第伍丹琲, 王虹, 陶红艳, 等. 鸦胆子素A通过EMT信号诱导非小细胞肺癌细胞凋亡. 中国药理学通报, 2024, 40(8): 1474-1481.
16. 冯亚婵, 张皓杰, 杜朝, 等. 青蒿素通过TIGIT/CD155信号轴调控4T1乳腺癌细胞转移与凋亡. 中国生物化学与分子生物学报, 2024, 40(1): 131-141.
17. Ding R, Wang Y, Xu L, et al. QiDongNing induces lung cancer cell apoptosis via triggering P53/DRP1-mediated mitochondrial fission. J Cell Mol Med, 2024, 28(9): e18353.
18. Wu Z, Xiao C, Li F, et al. Mitochondrial fusion-fission dynamics and its involvement in colorectal cancer. Mol Oncol, 2024, 18(5): 1058-1075.
19. Ding Y, Lv Z, Cao W, et al. Phosphorylation of INF2 by AMPK promotes mitochondrial fission and oncogenic function in endometrial cancer. Cell Death Dis, 2024, 15(1): 65.
20. Xiao J, Wang S, Chen L, et al. 25-Hydroxycholesterol regulates lysosome AMP kinase activation and metabolic reprogramming to educate immunosuppressive macrophages. Immunity, 2024, 57(5): 1087-1104.
21. Nath S, Patra D, Nag A, et al. Sesquiterpenoid-rich Java Ginger rhizome extract prompts autophagic cell death in cervical cancer cell SiHa mainly by modulating cellular redox homeostasis. 3 Biotech. 2023, 13(1): 8.
22. 鲁丁瑜, 廖建, 吴飞, 等. ECT2通过调控PI3K/AKT信号通路对胰腺癌细胞恶性行为、糖酵解及TH细胞分化的影响. 解剖学研究, 2023, 45(4): 329-336,341.
23. Egusquiza-Alvarez CA, Moreno-Londoño AP, Alvarado-Ortiz E, et al. Inhibition of Multifunctional Protein p32/C1QBP Promotes Cytostatic Effects in Colon Cancer Cells by Altering Mitogenic Signaling Pathways and Promoting Mitochondrial Damage. Int J Mol Sci, 2024, 25(5): 2712.

Chinese Journal of Respiratory and Critical Care Medicine

Latest ArticlesThe effects and mechanisms of mitochondrial fission mediated by mitochondrial dynamics related protein DRP1 on glucose metabolism reprogramming in lung cancer cells via PI3K/Akt signaling pathway

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