Fig 5.

Correlation of reduced DSG2 binding with the ability to open epithelial junctions. (A) Transepithelial electrical resistance (TEER) measured on polarized colon cancer T84 cells. Cells were cultured in transwell chambers until the TEER was constant, i.e., tight junctions had formed. A total of 5 μg of dimeric Ad3 fiber knobs in PBS was then added for 1 h to the apical chamber. TEER was measured at the indicated time points. n = 6. For time points 1.5 and 4 h, the difference between JO-1 and the D261N and N186D mutants was significant (P < 0.01). The arrows indicate the addition and removal of Ad3 fiber knobs. (B) Enhancement of irinotecan therapy. A total of 4 × 10⁶ A549 cells were injected subcutaneously into CB17-SCID/beige mice. Once the tumor reached a volume of ∼100 mm³ (day 15 after implantation), the mice were injected intravenously with 2 mg/kg JO-1, E299V, N186D, or PBS, followed by an intravenous injection of irinotecan (37.5 mg/kg) 1 h later. The treatment was repeated on day 25. n = 5. The differences between the irinotecan versus E299V plus irinotecan groups or irinotecan versus N186 plus irinotecan groups were not significant. The difference between irinotecan and JO-1 plus irinotecan was significant (P < 0.01) from day 20 on.