灵芝酸A通过调节AMPK/ULK1/mTOR通路对肺癌细胞凋亡和自噬的影响

doi:10.3969/j.issn.1006-6233.2025.05.01

Abstract
Figure/Table
References
Related Citation (1)

Download: PDF (0 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To investigate the effect of ganoderic acid A (GA-A) on apoptosis and autophagy in human lung cancer cells by mediating the adenosine 5'-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway. Methods: The Cell Counting Kit (CCK-8) was used to detect the toxicity of GA-A (0-160 μM) on A549 cells. A549 cells were assigned into control group (Ctrl), low-dose GA-A group (GA-A-L, 40 μM), high-dose GA-A group (GA-A-H, 80 μM), and high-dose GA-A+AMPK inhibitor group (GA-A-H+compound C). The colony formation experiment was used to detect cell proliferation ability. Flow cytometry was used to detect apoptosis in A549 cells. MTT method was used to detect cell proliferation; Western blot was used to detect the expression levels of apoptosis, autophagy, and AMPK/ULK1/mTOR pathway-related proteins in A549 cells. Results: Compared with the 0 μM group, the proliferation inhibition rate of A549 cells in the GA-A treatment groups was prominently higher (P<0.05), and the IC50 of GA-A on A549 cells was 81.44 μM. Compared with the control group, the A549 cell survival rate, colony formation rate, Bcl-2 and p62 protein expression, and p-mTOR/mTOR level were prominently lower in the GA-A-L and GA-A-H groups (P<0.05), while the apoptosis rate, number of autophagosomes, Bax protein expression, and LC3B-II/I, p-AMPK/AMPK, and p-ULK1/ULK1 levels were prominently higher (P<0.05). Compared with the GA-A-H group, the cell survival rate, colony formation rate, Bcl-2 and p62 protein expression, and p-mTOR/mTOR level were prominently higher in the GA-A-H+compound C group (P<0.05), while the apoptosis rate, number of autophagosomes, Bax protein expression, and LC3B-II/I, p-AMPK/AMPK, and p-ULK1/ULK1 levels were prominently lower (P<0.05). Conclusion: GA-A may induce apoptosis and autophagy in human lung cancer cells and inhibit cell proliferation by regulating the expression of key proteins in the AMPK/ULK1/mTOR pathway.

Key words： Lung cancer cells Ganoderic acid A Adenosine 5'-monophosphate-activated protein kinase/unc-51-like autophagy-activating kinase/mammalian target of rapamycin pathway

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.05.01 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I5/705

[1] Ma F,Wang J,Jiang W,et al.Ganoderic acid A:a potential natural neuroprotective agent for neurological disorders:a review[J].Int Med Mushrooms,2024,26(2):11-23.
[2] Gong E,Pan J,Ye Z,et al.Ganoderic acid A suppresses autophagy by regulating the circFLNA/miR-486-3p/CYP1A1/XRCC1 axis to strengthen the sensitivity of lung cancer cells to cisplatin[J].Pharm Pharmacol,2024,76(4):354-367.
[3] Rahman MA,Rahman MDH,Hossain MS,et al.Molecular insights into the multifunctional role of natural compounds:autophagy modulation and cancer prevention[J].Biomedicines,2020,8(11):517.
[4] Debnath J,Gammoh N,Ryan KM.Autophagy and autophagy-related pathways in cancer[J].Nat Rev Mol Cell Biol,2023,24(8):560-575.
[5] Zhu LH,Liang YP,Yang L,et al.Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines[J].Integr Med,2024,22(4):503-514.
[6] Zheng Z,Bian Y,Zhang Y,et al.Metformin activates AMPK/SIRT1/NF-κB pathway and induces mitochondrial dysfunction to drive caspase3/GSDME-mediated cancer cell pyroptosis[J].Cell Cycle,2020,19(10):1089-1104.
[7] Xia J,Dai L,Wang L,et al.Ganoderic acid A alleviates hypoxia-induced apoptosis,autophagy,and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways[J].Phytother Res,2020,34(8):2082.
[8] Li J,Fan Y,Zhang Y,et al.Resveratrol induces autophagy and apoptosis in non-small-cell lung cancer cells by activating the NGFR-AMPK-mTOR pathway[J].Nutrients,2022,14(12):2413.
[9] Song J,Liu J,Cui C,et al.Mesenchymal stromal cells ameliorate diabetes-induced muscle atrophy through exosomes by enhancing AMPK/ULK1-mediated autophagy[J].Cachexia Sarcopenia Muscle,2023,14(2):915-929.
[10] Zhou GZ,Wang QQ,Wang PB,et al.One novel curcumin derivative ZYX01 induces autophagy of human non-small lung cancer cells A549 through AMPK/ULK1/Beclin-1 signaling pathway[J].Cell Mol Biol (Noisy-le-grand),2019,65(2):1-6.