Figure 3.

Therapeutic silencing of Bcl-2 by NL-Bcl-2 siRNA inhibits in vivo tumor growth of ER(−) MDA-MB-231 xeonografts in nude mice. (a) Mice were orthotopically injected into mammary fat pat with luciferase-expressing MDA-MB-231 cells. Mice-bearing tumors with equal size were randomly assigned into control and treatment groups (n = 5 mice per group). Mice received either NL-Bcl-2 siRNA or NL-control siRNA treatments (0.15 mg siRNA/kg or 4 µg/mouse, i.v, twice a week) from tail vein for 4 weeks (total of eight injections). After 4-weeks of treatments, mice were imaged following luciferin injection (i.p.) by Xenogen-IVIS live-imaging system under anesthesia. (b) Therapeutic silencing of Bcl-2 by NL-Bcl-2 siRNA enhances the antitumor efficacy of doxorubicin. Mice were treated with NL-Bcl-2-siRNA or NL-control siRNA (0.15 mg siRNA/kg, i.v, twice a week) and also received doxorubicin (4 mg/kg, i.p, once a week) for 4 weeks and imaged. (c) Mice that were treated with NL-Bcl-2 siRNA had significantly reduced tumor weight compared with the control group that was treated with NL-Control siRNA. Enhanced the antitumor efficacy of doxorubicin was observed when combined with NL-Bcl-2 siRNA. The tumor weights were measured 4 weeks of treatments shown in Figure 3a, b. (d) Bcl-2 protein expression after 4 weeks of treatments in MDA-MB-231 tumors. After sacrificing mice, tumors were removed (48 hours after the last treatment) and tumor lysates were analyzed for Bcl-2 expression by western blot. (e) NL-Bcl-2-siRNA treatment was well tolerated and did not cause weight lose in mice, compared with those that received NL-control siRNA. Mice that received doxorubicin had slight reduced weight loss compared with those that did not receive chemotherapy. (f) In vitro silencing of Bcl-2 by siRNA treatment increases the antiproliferative effects of paclitaxel and inhibit colony formation of MDA-MB-231 cells.