Abstract
Abstract Purpose; To investigate whether the Abraxane loaded within Multi-Stage Nanovector (MSV) system (MSV-ABX) is more effective in therapy of liver metastases of breast and lung cancer as compared to Abraxane (ABX). Experimental Design; MTT assay was performed to evaluate sensitivity of 4T1, murine breast cancer cells and 3LL, murine lung cancer cells to ABX or MSV-ABX in vitro. Experimental liver metastases were produced by intra-splenic injection of 4T1 or 3LL cells in Balb/C mice. The mice bearing liver metastases were treated with intravenous injection of (1) control (PBS), (2) ABX or (3) MSV-ABX. Then the mice were sacrificed and liver weight was measured to evaluate the therapeutic efficacy. To evaluate the biological the effects of therapeutics, we performed histological and immunohistochemical analysis of the tumor specimens. Apoptosis of 4T1 and 3LL tumor cells were evaluated by TUNEL staining, and proliferation of the tumor cells were stained using antibody to Ki67. Tumor diameter was measured in H&E stained sections. Results; There was no significant difference in the sensitivity of 4T1 and 3LL cancer cells to ABX and MSV-ABX, in vitro. All the mice injected with 4T1 or C3LL cells developed multiple liver metastases. The liver weight was significantly lower in the mice treated with MSV-ABX as compared to those in the other groups. The tumor diameters in the liver were significantly smaller in the mice treated with MSV-ABX as compared to those in the other two groups. Immunofluorescent analysis revealed that MSV-ABX inhibited proliferation and increased apoptosis of 4T1 and 3LL tumor cells in the liver significantly more than ABX.Conclusions; These studies demonstrate that MSV-ABX is more effective than ABX in therapy of the liver metastasis of breast and colorectal cancer in our mouse models. These data can be translated into the clinic for planning novel clinical trials using MSV-ABX. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-04-21.
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