Figure 4

Pitavastatin and irinotecan exhibit synergism in terms of inducing GBM cell death in vitro . (A) U87 IC₅₀ values for various compounds with and without pitavastatin (2 μM), note that irinotecan IC₅₀ was reduced by 50%. (B) Pitavastatin, sharply lowered the IC₅₀ of irinotecan in U118, U87 cells and SK72. The combination index calculated at ED₅₀, ED₇₅ and ED₉₀. Data were calculated at two pitavastatin concentrations. (C) Escalation of apoptosis by addition of pitavastatin to irinotecan, particularly after 12 hours of incubation. (D) Pitavastatin and irinotecan applied singly induce MDR-1 mRNA transcription as shown by qRT-PCR, and when applied together the level of transcription is only slightly greater than with irinotecan alone. (E) Western blot analysis indicating that after irinotecan treatment, U87 expressed full length MDR-1 (170 KD), but in combination with pitavastatin, the band density of unglycosylated MDR-1 (140 KD) increased dramatically. Unglycosylated MDR-1 cannot be transported inside the cell and is essentially non-functional. (F) After pitavastatin treatment, U87 cell and SK72 cells were accumulated more Calcein AM and showed higher fluorescent signal than control by inhibited the MDR-1 function.