The expression of androgen receptor variant (ARV) in castration resistant prostate cancer cells was an important factor in determining the therapeutic response. Despite 2D cultures being widely used for these response, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of physiologic response. While generally more complicated, 3D culture systems provide a better cancer architecture and a more accurate drug response. We compared the expression of ARV in 2D and 3D culture of castration resistant prostate cancer cell after anti-cancer therapy.
Monolayer (2D) and 3D cultures were performed using PC3 cell, and control and curcumin (30uM) group were established. The authors designed and fabricated a calcium-free, physically crosslinked, efficient, and bioactive hydrogel composed of alginate, marine collagen, and agarose (AmCA) for use in 3D cell cultures. After 3 days, the mRNA expression of AR and ARV1 were compared using real-time polymerase chain reaction.
The mRNA expression of AR decreased 31% and 54% after curcumin treatment in both 2D and 3D cultures. (figure) The mRNA of ARV1 was not expressed in 2D culture, however, was clearly expressed in control and curcumin groups in 3D culture.(p<0.001) Especially, the mRNA expression of ARV1 increased more under curcumin (100%) than control group (86%).(p<0.05)
In the 3D cell culture using AmCA, genetic change of AR and its variants occurred more frequently after curcumin treatment. The mRNA expression of ARV1, which was not observed in 2D culture, increased markedly in 3D culture. The mRNA expression of ARV1 was further increased under curcumin, compared to control group. Collectively, the results showed that 3D cell culture models strongly influences cellular behaviors, the response using 3D cell culture to the chemotherapeutic drug is more consistent with in vivo results than the equivalent 2D controls.