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Published on: August 4, 2022
Acidic stress induces protective autophagy in SGC7901 cells
Jie Sheng1, Li-Bin Sun1, Shu-Fen Zhao1
11 Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
Abstract:
Objective To investigate the effect of acidity on gastric cancer SGC7901 cells in terms of autophagy and provide a new strategy for therapeutically targeting gastric cancer autophagy in an acidic environment. Methods Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used to examine the effect of an acidic environment on autophagosome formation. Light chain 3 (LC3) and p62 levels in SGC7901 cells exposed to acidic conditions were measured using Western blot analysis. To explore changes in autophagy flux, the cells were treated with an inhibitor of autophagy bafilomycin A1. The CCK-8 assay was performed to determine if inhibiting acid-induced autophagy affected cell proliferation. Results Increased autophagosome formation was observed by TEM. Punctate LC3 structures were observed in cells cultured under acidic conditions, whereas untreated cells exhibited diffuse and weak staining for punctate LC3 structures. Cytoplasmic LC3-I translocated to the autophagic membrane (LC3-II) levels increased under acidic conditions, whereas p62 levels decreased. The bafilomycin A1-induced inhibition of autophagy caused by the acidic environment inhibited cell proliferation. Conclusion The acidic environment upregulates autophagy in SGC7901 cells. In long-term culture, a stable and high level of autophagy is maintained in an acidic environment, which has a protective effect on cells.
Insights
An acidic environment enhances autophagy in gastric cancer cells, promoting cell survival. Inhibiting this acid-induced autophagy could offer a new therapeutic strategy for targeting gastric cancer.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Gastric cancer is a significant global health concern.
- The tumor microenvironment, including acidity, influences cancer cell behavior.
- Autophagy plays a complex role in cancer progression and treatment resistance.
Purpose of the Study:
- To investigate the impact of acidity on autophagy in gastric cancer SGC7901 cells.
- To explore the potential of targeting autophagy in acidic environments for gastric cancer therapy.
Main Methods:
- Transmission electron microscopy (TEM) and confocal laser scanning microscopy for autophagosome visualization.
- Western blot analysis to quantify autophagy markers Light chain 3 (LC3) and p62.
- Bafilomycin A1 treatment to assess autophagy flux and CCK-8 assay for cell proliferation.
Main Results:
- Acidic conditions significantly increased autophagosome formation and LC3-II levels, indicating upregulated autophagy.
- A decrease in p62 levels was observed under acidic conditions.
- Inhibition of acid-induced autophagy by bafilomycin A1 suppressed SGC7901 cell proliferation.
Conclusions:
- The acidic tumor microenvironment upregulates autophagy in gastric cancer cells.
- Sustained high autophagy levels in acidic conditions provide a protective effect on cancer cells.
- Targeting acid-induced autophagy presents a potential therapeutic strategy for gastric cancer.
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