Effects of Icodextrin Solution (Adept®) on Ovarian Cancer Cell Proliferation in an In Vitro Model

Abstract

Background and objective: Anti-adhesion barriers are currently used during ovarian cancer surgery to decrease adhesion-related morbidity. Adept^® (4% icodextrin) solution, a liquid anti-adhesion material, has been widely used during gynecologic surgeries, though the risk of this barrier for oncologic surgery is controversial. The aim of this study was to determine the effect of Adept^® solution on the proliferation of ovarian cancer cells. Materials and methods: We assessed the dose- and time-dependent effects of icodextrin on the growth and proliferation of OVCAR-3 and A2780 human ovarian tumor cell lines in vitro. Cell growth was determined by cell number counting. Expressions of cell cycle-regulation proteins (cyclin D1 and cyclin B1) were determined using Western blot analysis. Results: Adept^® did not significantly increase ovarian cancer cell growth when tested at various concentrations (0, 1, 5, 10, 15, and 20%, equal to 0, 0.04, 0.2, 0.4, 0.6 and 0.8% icodextrin) and different time points (1-3 days) compared to control cells. Moreover, the protein levels of cyclin D1 and B1 were not overexpression-elevated in icodextrin-treated ovarian cancer cells, either with an increasing concentration or with an increasing treated time. These results demonstrated that Adept^® does not activate the growth or proliferation of ovarian cancer cells in either a dose- or time-dependent manner. Conclusions: This study supports the use of Adept^® solution as a safe anti-adhesion barrier for ovarian cancer surgery, though further in vivo studies are necessary.

Keywords: Adept®; anti-adhesion barrier; cell proliferation; cyclin; icodextrin; ovarian cancer.

Figure 1

Various concentrations of Adept^® solution do not affect OVCAR-3 and A2780 cell growth and proliferation. (A) OVCAR-3 and (B) A2780 cells were plated in six-well plates at 1.1 × 10⁴ cells/cm² and 5.6 × 10³ cells/cm², respectively, in regular medium for 3 days, then incubated in 1, 5, 10, 15 or 20% Adept^® (equal to 0, 0.04, 0.2, 0.4, 0.6 and 0.8% icodextrin) solution for 3 days; control cells were cultured in medium alone. After treatment for 3 days, cells were trypsinized and total live cell numbers were counted. The ratio of cell growth was calculated by normalizing the numbers of treated cells to the number of control cells (n = 3 × 2). Total cell lysates from (C) OVCAR-3 and (D) A2780 cells treated with various concentrations of Adept^® solution were subjected to Western blot analysis to quantify the cell cycle regulation proteins cyclin B1 and cyclin D1; β-actin was used as a loading control.

Figure 2

Adept^® solution does not affect OVCAR-3 and A2780 cell growth and proliferation at various time-points. (A) OVCAR-3 and (B) A2780 cells were plated in six-well plates in triplicate at 1.1 × 10⁴ cells/cm² and 4 × 10³ cells/cm², respectively, in regular medium for 3 days, then 10% Adept^® solution (v/v, equal to 0.4% icodextrin) was added; control cells were cultured in regular medium alone. Triplicate samples were harvested after 1, 2 or 3 days of icodextrin treatment, and then cells were trypsinized. Total live cell numbers were counted. The ratio of cell growth was calculated by normalizing the numbers of treated cells to the number of control cells (n = 3 × 2). Total cell lysates from (C) OVCAR-3 and (D) A2780 cells at various time points were subjected to Western blot analysis to quantify the cell cycle regulation proteins cyclin B1 and cyclin D1; β-actin was used as a loading control.