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Chinese Journal of Oncology Prevention and Treatment ›› 2023, Vol. 15 ›› Issue (3): 291-297.doi: 10.3969/j.issn.1674-5671.2023.03.07

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Bisdemethoxycurcumin induces apoptosis and inhibits proliferation of non-small cell lung cancer cells by regulating HIF-1α-mediated senescence

  



  • Online:2023-06-25 Published:2023-06-19

Abstract: Objective To investigate the regulatory effect of dimethoxycurcumin (BDMC) on the proliferation and apoptosis in non⁃small cell lung cancer cells and its mechanism. Methods Non⁃small cell lung cancer cell lines NCI⁃H1975 and NCI⁃H520 were treated with phosphate buffered saline (PBS) and 20 μmol/L BDMC. Cell viability was detected by CCK⁃8; cell proliferation was detected by carboxyfluorescein diacetate succinimide ester (CFSE); cell apoptosis was detected by acridine orange (AO) and Annexin V⁃FITC/PI staining; senescence⁃associated β⁃galactosidase (SA⁃β⁃Gal) staining assay was used to detect the activity of SA⁃β⁃Gal; the proportion of  SA⁃β⁃Gal positive cells was detected by flow cytometer. Subsequently, NCI⁃H1975 and NCI⁃H520 cells were treated with 20 μmol/L BDMC, 20 μmol/L hypoxia inducible factor⁃1α (HIF⁃1α) inhibitor PX⁃478, or a combination of both, respectively, and the cells treated with PBS served as the control group. The expression of HIF⁃1α and HIF⁃2α proteins was detected by Western blot , and the activity of SA⁃β⁃Gal was detected by SA⁃β⁃Gal staining assay. Results Compared with the PBS group, the cell viability of NCI⁃H1975 and NCI⁃H520 in BDMC group was significantly reduced (all P<0.05), the proportion of CFSE⁃positive proliferating cells was significantly reduced (all P<0.01), the number of AO⁃positive cells was significantly decreased (all P<0.01), the proportions of Annexin V+PI- cells and SA⁃β⁃Gal+PI- cells were significantly increased (all P<0.01), the SA⁃β⁃Gal activity was significantly increased (all P<0.001), the protein expression of HIF⁃1α was significantly increased (all P<0.001). Compared with BDMC group, the protein expression of HIF⁃1α in BDMC+PX⁃478 group were decreased (P<0.05), as well as the proportion of SA⁃β⁃Gal⁃positive cells. Conclusions BDMC may promote senescence of non⁃small cell lung cancer cells by up⁃regulating HIF⁃1α signaling pathway, and thus inhibit cell proliferation and promote apoptosis.

Key words:  Non?small cell lung cancer, Dimethoxycurcumin, Senescence, Proliferation, Apoptosis, Hypoxia inducible factors

CLC Number: 

  • R734.2