Literature Spotlight: Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells

A paper published in the Open Access Journal of Scientific Reports examined the relationship between occludin expression and chemoresistance of A549 cells grown in both traditional (2D) and spheroid (3D) culture setups. They also used Visikol HISTO-M to clear their spheroids for microscopy.

Background

A549 cells are a cell line used for modeling adenocarcinoma, a non-small cell lung cancer. Non-small cell lung cancer accounts for 80% of diagnosed lung cancers and is typically treated with Cisplatin. 50% of patients who undergo treatment acquire a chemo resistant disease phenotype which creates barriers to successful treatment. The underlying mechanisms behind developed chemoresistance are still poorly understood and more information would allow for a more targeted chemotherapeutic treatment.

In a previous paper the group reported an increase in claudin 1 and 2 expression corelating to a decrease in A549 sensitivity to doxorubicin. This led to the investigation into occludin, another tight junction protein, and its effects on chemoresistance. The chemoresistant A549 cell lines displayed an increased level of occludin expression. Normal A549 cells were induced to overexpress occludin. When grown in 2D the overexpression did not result in a decrease in chemosensitivity, but the same cells grown in 3D had a decrease in sensitivity. That decrease in sensitivity and increase in occludin expression was reversible with application of LY-294002, an Akt inhibitor. Implicating the PI3K/Akt signaling pathway. Occludin knockdown in spheroids using siRNA also showed an increase in chemo sensitivity. Further strengthening the connection between occludin expression and chemo resistance.

Conclusion

Broadly, this work shows how 3D cell culture can result in physiologically useful models of important biological systems that might not be recapitulated as accurately in 2D cell culture. Specifically, it indicates the PI3K/Akt pathway for investigation for valid adjuvant therapy targets.

References

  1. Hiroaki Eguchi et al. Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells. Scientific Reports 8, 15157 (2018) https://www.nature.com/articles/s41598-018-33566-w
2019-04-10T10:49:28-05:00
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