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Research on the mechanism of hypoxia promoting the migration of lung adenocarcinoma A549 cells / 中国应用生理学杂志
Chinese Journal of Applied Physiology ; (6): 68-74, 2022.
Article in Chinese | WPRIM | ID: wpr-927900
ABSTRACT

Objective:

To investigate the mechanism that hypoxia promotes the migration of lung adenocarcinoma A549 cells.

Methods:

A549 cells were cultured and cells that knockdown of acetyl-CoA carboxylase 1 (ACC1) were obtained by transfection with lentivirus, and cells that knockdown of sterol regulatory element-binding proteins-1 (SREBP-1) were obtained by treated with si-RNA. A549 cells were treated with hypoxia combined with hypoxia inducible factor-1α (HIF-1α) inhibitor PX-478 (25 μmol); Hypoxia combined with linoleic acid (LA) (20 μmol) treated A549 cells with ACC1 knockdown, and A549 cells with SREBP-1 knockdown were treated by hypoxia. Transwell migration assay was used to detect cell migration. Western blot was conducted to detect HIF-1α, ACC1 and epithelial mesenchymal transition (EMT) related proteins, Vimentin, E-Cadherin and SREBP-1; Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was performed to detect the changes of ACC1 and SREBP-1 mRNA in A549 cells after hypoxia and HIF-1α inhibitor PX-478 (25 μmol) treatment. Each experiment was repeated three times.

Results:

Compared with the normoxic control group, hypoxia promoted the migration of A549 cells (P<0.01), and up-regulated the expressions of ACC1, HIF-1α (all P<0.01) and SREBP-1 (P<0.05). PX-478 (25 μmol) inhibited the migration of A549 cells induced by hypoxia and down-regulated the expression of SREBP-1 (all P<0.05). ACC1 mRNA and SREBP-1 mRNA levels were increased after hypoxia treatment of A549 cells (all P<0.05). The levels of ACC1 mRNA and SREBP-1 mRNA were decreased after A549 cells treated with hypoxia combined with PX-478 (25 μmol) for 24 h (P<0.05, P<0.01). Knockdown of SREBP-1 in A549 cells was obtained by transfection with si-RNA. Transwell migration assay showed the number of cell migration in si-SREBP-1 group was less than that in normoxia control group (P<0.01). The si-SREBP-1 group and the si-NC group were treated with hypoxia. Compared with the control group, the number of cell migration in the si-SREBP-1 group was decreased (P<0.01), however, the difference was not statistically significant compared with the normoxia si-SREBP-1 group (P>0.05). Western blot showed that the expression of ACC1 in the si-SREBP-1 group was lower than that in the control group (P<0.01). Compared with the control group, the expression of ACC1 was decreased after si-SREBP-1 group treated with hypoxia (P<0.01). Knockdown of ACC1 inhibited the migration of A549 cells (P<0.05). After knockdown of ACC1, the migration number of A549 cells under normoxia and 5% O2 conditions had no significant difference (P>0.05). Application of LA under hypoxia condition rescued ACC1-knockdown induced inhibitory effect on hypoxia-promoted A549 cell migration (P<0.05).

Conclusion:

Hypoxia promotes migration of lung adenocarcinoma A549 cells by regulating fatty acid metabolism through HIF-1α/SREBP-1/ACC1 pathway.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Acetyl-CoA Carboxylase / RNA / RNA, Messenger / Cell Hypoxia / Cell Line, Tumor / Sterol Regulatory Element Binding Protein 1 / Hypoxia-Inducible Factor 1, alpha Subunit / A549 Cells / Adenocarcinoma of Lung / Lung Neoplasms Limits: Humans Language: Chinese Journal: Chinese Journal of Applied Physiology Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Acetyl-CoA Carboxylase / RNA / RNA, Messenger / Cell Hypoxia / Cell Line, Tumor / Sterol Regulatory Element Binding Protein 1 / Hypoxia-Inducible Factor 1, alpha Subunit / A549 Cells / Adenocarcinoma of Lung / Lung Neoplasms Limits: Humans Language: Chinese Journal: Chinese Journal of Applied Physiology Year: 2022 Type: Article