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.
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2025, Vol. 31 
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