Related Experiment Video
Updated: Jun 26, 2026
In Vitro Scratch Assay to Demonstrate Effects of Arsenic on Skin Cell Migration
Published on: February 23, 2019
Increased aquaglyceroporin 9 expression disrupts arsenic resistance in human lung cancer cells
Zhi-Feng Miao1, Eddy Essen Chang, Feng-Yuan Tsai
1Laboratory of Molecular Toxicology, Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
Abstract:
Resistance to chemotherapy is one of the major problems in treatment responses of lung cancer. This study explored the mechanism underlying the arsenic resistance of lung cancer. Four lung cancer cells with different proliferation activity were characterized for cytotoxicity, arsenic influx/efflux, and arsenic effects on intracellular glutathione and 8-hydroxy-2'-deoxyguanosine (8-OHdG) production. Our data revealed that relative proliferation potency of these cells was H1299>A549>CL3>H1355. Moreover, A549, H1299, and H1355 were markedly resistant to As(2)O(3) with IC50 approximately 100 microM, whereas CL3 was sensitive to As(2)O(3) with IC50 approximately 11.8 microM. After treatment with the respective As(2)O(3) at IC50, arsenic influx/efflux activity in CL3 was comparable to those in the other three arsenic-resistant cells. However, differences in glutathione levels and 8-OHdG production were also detected either before or after arsenic treatment, indicating that a certain degree of variation in anti-oxidative systems and/or 8-OHdG repair activity existed in these cell lines. By transfection of an aquaglyceroporin 9 (AQP9) gene, we showed that increased AQP9 expression significantly enhanced arsenic uptake and disrupted arsenic resistance of A549. The present study strongly suggests that membrane transporters responsible for arsenic uptake, such as AQP9, may play a critical role in development of arsenic resistance in human lung cancer cells.
Insights
Lung cancer cells exhibit resistance to arsenic (As2O3) due to variations in anti-oxidative systems and DNA repair. Increased aquaglyceroporin 9 (AQP9) expression enhances arsenic uptake, overcoming resistance.
Area of Science:
- Oncology
- Molecular Biology
- Toxicology
Background:
- Chemotherapy resistance is a significant challenge in lung cancer treatment.
- Understanding the mechanisms of arsenic resistance is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the underlying mechanisms of arsenic resistance in human lung cancer cells.
- To identify potential molecular targets for overcoming arsenic resistance.
Main Methods:
- Characterization of four lung cancer cell lines for cytotoxicity, arsenic transport, glutathione levels, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) production.
- Assessment of arsenic influx/efflux activity and its correlation with resistance.
- Gene transfection to evaluate the role of aquaglyceroporin 9 (AQP9) in arsenic uptake and resistance.
Main Results:
- Lung cancer cell lines displayed varying sensitivities to arsenic trioxide (As2O3), with IC50 values ranging from 11.8 microM (CL3) to approximately 100 microM (A549, H1299, H1355).
- Arsenic influx/efflux rates were comparable across resistant and sensitive cell lines, suggesting other factors contribute to resistance.
- Differences in intracellular glutathione levels and 8-OHdG production indicated variations in anti-oxidative and DNA repair capacities.
- Overexpression of AQP9 significantly increased arsenic uptake and reversed arsenic resistance in A549 cells.
Conclusions:
- Membrane transporters, particularly AQP9, play a critical role in arsenic uptake and the development of arsenic resistance in human lung cancer.
- Variations in cellular anti-oxidative systems and DNA repair mechanisms also contribute to arsenic resistance.
- Targeting membrane transporters like AQP9 presents a potential strategy to enhance the efficacy of arsenic-based therapies in lung cancer.
Related Concept Videos
01:25Aquaporins
01:28Gene Regulation in Microbial Communities: Quorum Sensing