Abstract：Objective: To investigate the effects of theaflavin on A549 cell proliferation, apoptosis, and autophagy by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway.Methods: The proliferation rate of A549 cells was measured after intervention with 0, 2.5, 5, 10, 20, 40, 80, and 160 μmol/L theaflavin, and the appropriate concentration of action was screened. A549 cells were separated into control group, low theaflavin group (20 μmol/L theaflavin), medium theaflavin group (40 μmol/L theaflavin), high theaflavin group (80 μmol/L theaflavin), and high theaflavin+740Y-P group (80 μmol/L theaflavin+30 μmol/L PI3K/Akt/mTOR signaling pathway activator 740Y-P). CCK-8 method and plate colony formation experiment were applied to determine the proliferation of A549 cells. Flow cytometry and MDC methods were applied to determine apoptosis and autophagic vacuole formation in A549 cells, respectively. Western blot was applied to determine the expression of PI3K/Akt/mTOR signaling pathway proteins and autophagy proteins in A549 cells.Results: Compared with 0 μmol/L of theaflavin, 2.5, 5, 10, 20, 40, 80, and 160 μmol/L of theaflavin can inhibit the proliferation of A549 cells. The IC50 value of theaflavin on A549 cells was calculated to be 36.72 μmol/L. Compared with the control group, the proliferation rate, colony formation rate, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR of A549 cells in the low theaflavin group, medium theaflavin group, and high theaflavin group all reduced, the apoptosis rate, relative content of autophagic vacuoles, LC3II/LC3I, and Beclin-1 protein expression all increased, and all showed dose-dependent changes in theaflavin (P<0.05). Compared with the high theaflavin group, the proliferation rate, colony formation rate, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR of A549 cells in the high theaflavin+740Y-P group all increased, the apoptosis rate, relative content of autophagic vacuoles, LC3II/LC3I, and Beclin-1 protein expression all reduced (P<0.05).Conclusion: Theaflavin can induce protective autophagy by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway, thereby promoting apoptosis and inhibiting the proliferation of lung cancer cells.
[1] Fu B,Zhou F,Zhang J,et al.Sevoflurane attenuates proliferative and migratory activity of lung cancer cells via mediating the microRNA-100-3p/sterol O-Acyltransferase 1 axis[J].Chin Physiol,2023,66(6):456-465. [2] Shi S,Ma B,Sun F,et al.Theaflavin binds to a druggable pocket of TMEM16A channel and inhibits lung adenocarcinoma cell viability[J].Biol Chem,2021,297(3):101016. [3] Yang C,Yaolin S,Lu W,et al.G-protein signaling modulator 1 promotes colorectal cancer metastasis by PI3K/AKT/mTOR signaling and autophagy[J].Int Biochem Cell Biol,2023,157(2):106388-106395. [4] Zhang Z,Bi X,Lian X,et al.BDH1 promotes lung cancer cell proliferation and metastases by PARP1-mediated autophagy[J].Cell Mol Med,2023,27(7):939-949. [5] Xu J,Wang SJ,Bu SS,et al.Theaflavin promoted apoptosis in nasopharyngeal carcinoma unexpectedly via inducing autophagy in vitro[J].Iran Basic Med Sci,2022,25(1):68-74. [6] 孙绪高,杨文超,刘彦杰,等.茶黄素调节Snail/Slug信号通路对口腔鳞癌细胞生物学行为的影响[J].天津医药,2023,51(11):1164-1170. [7] Imran A,Butt MS,Xiao H,et al.Inhibitory effect of black tea (Camellia sinensis) theaflavins and thearubigins against HCT 116 colon cancer cells and HT 460 lung cancer cells[J].Food Biochem,2019,43(5):12822-12831. [8] Zhao L,Wu X,Zhang Z,et al.ELF1 suppresses autophagy to reduce cisplatin resistance via the miR-152-3p/NCAM1/ERK axis in lung cancer cells[J].Cancer Sci,2023,114(6):2650-2663. [9] 吕波,佟剑虹.重楼皂苷Ⅰ通过JNK信号通路诱导乳腺癌细胞凋亡和自噬[J].世界科学技术-中医药现代化,2022,24(3):1166-1173. [10] 刘然,邢爽,王璐,等.千金藤素通过调控p53信号介导的自噬逆转人非小细胞肺癌细胞的埃克替尼耐药性[J].临床肺科杂志,2022,27(5):744-750,772. [11] 曹雪婷,吴博雅,陈静.刺五加苷B介导PI3K/Akt/mTOR通路诱导肺癌细胞凋亡和自噬[J].中国中药杂志,2023,48(24):6693-6701. [12] Zhou J,Jiang YY,Chen H,et al.Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway[J].Cell Prolif,2020,53(2):12739-12751.
2024, Vol. 30 
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