Effects of GCS Silencing on P-gp Regulated Drug Accumulation and Efflux in Tumors. NCI/ADR-RES tumors were treated with MBO-asGCS (1 mg/kg/3 days, 3 mice/group) or saline for 7 days. (A) Doxorubicin accumulation. After 4 hr and 24 hr peritoneal administration of doxorubicin (1 mg/kg), serum and tumor tissues were collected and prepared for HPLC assays. Doxorubicin levels were represented per μl of serum or per mg of tumor tissue. *, p < 0.001 compared with serum of saline treatment at 24 hr; **, P < 0.001 compared with saline treatments. (B) Paclitaxel accumulation. After two administrations of MBO-asGCS, tissue suspensions (25 mg/reaction) were incubated with Flutax-2 (1 μM) in medium containing collagenase IV, immediately following mincing. Accumulation of paclitaxel was measured after 2 hr incubation. *, p < 0.001 compared with saline treatment of tumors. (C) Paclitaxel efflux. After accumulation described in (B), tissues were incubated with fresh medium for an additional 2 hr to measure paclitaxel efflux. *, p < 0.001 compared with saline treatment of tumors.