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. Author manuscript; available in PMC: 2013 Mar 15.
Published in final edited form as: Toxicon. 2011 Feb 24;59(4):472–486. doi: 10.1016/j.toxicon.2011.02.020

Figure 6. The anti-tumor activity of liposomal VCN (LVCN) in MDA-MB-231 breast carcinoma xenograft model.

Figure 6

Nude mice inoculated orthotopically (mammary fat pads; 2.5×106 cells) were allowed to grow palpable tumors before treatment was commenced (indicated by the arrow). Two different liposomal formulation of VCN were tested in this study: LVCN-S (prepared by sonication) and LVCN-H (prepared by homogenization). The groups of animals (n=10) were treated intravenously with either LVCN-H or LVCN-S (the dose-equivalent of 100μg of VCN per injection) each administered twice a week, or Avastin (400μg per injection; approx. 20μg/gr) administered once a week. The control group received empty liposomes only. When compared to the control group, a significant delay in tumor growth (i) and increased survival (ii) was observed in all treated groups. ANOVA was used for statistical analysis followed by Dunnett’s multiple comparison tests (** signifies a P<0.001). (iii) In a different study, designed to assess the ability of VCN to induce tumor apoptosis, MDA-MB-231 xenografts were allowed to grow to a significantly larger volume (4 weeks after inoculation) before the treatments were initiated. These animals received 6 consecutive doses of either LVCN (at the dose-equivalent of 100μg of VCN per injection) or Avastin (400μg per injection) administered intravenously every other day and compared to a control group that received saline only. Tumor cryostat sections from each group were stained with FITC-TUNEL, and counterstained with Hoechst 33342. Representative confocal images from multiple experiments taken at x250 magnification are shown above (scale bar, 100μm; panels A1-C1 - TUNEL-Hoechst, panels A2-C2 - TUNEL only). (iv) The amount of cell death was quantitated as ‘number of TUNEL+ nuclei/total number of nuclei x 100’ by counting all nuclei in ‘hotspot’ areas from multiple fields using a computer-assisted approach (the ‘SimplePCI’ imaging software). The LVCN group shows a significantly increased amount of cell death compared to either Avastin or PBS control. The data was analyzed with ANOVA followed by post-hoc tests (* signifies a P<0.01).