Local injection of liposomal adriamycin to inhibit metastatic cell proliferation in axillary nodes in rabbits bearing breast tumors

Objective: To assess the inhibitory effects of local injection of liposomal adriamycin (LADR) on the proliferation of lymph node metastases in rabbits bearing VX2 carcinoma in the mammary gland. Methods:Thirty female New Zealand white rabbits were divided into 3 groups, with 10 in each. VX2 tumor mass suspensions were injected into the breast tissues of rabbits. Treatment initiated once the axillary lymph node reached 5 mm in the maximum diameter. Group 1 received a sham treatment. Group 2 received a subcutaneous injection of LADR adjacent to tumor. Group 3 received an intravenous injection of free ADR (FADR) at the same dose and concentration to group 2. The breast tumors and axillary lymph nodes were resected after the treatment was repeated 3 times. The tumor and node sizes before and after treatment were measured. PCNA mRNA expressions in breast tumors and axillary nodes were determined using RT-PCR. Results: The mean growth ratios of lymph nodes after treatment were 3. 70, 1. 55, and 2. 89,respectively, in groups 1,2, and 3. The slowest node growth was observed in animals of group 2, with significant differences from group 1 (P<0. 001) and group 3 (P = 0. 002). The relative values of PCNA mRNA expression in lymph nodes were 0. 541, 0. 329,and 0. 450, respectively, in groups 1,2, and 3. Group 2 exhibited a significantly reduced PCNA mRNA expression in metastatic lymph node, as compared to group 1 (P<0. 001) and group 3 (P = 0. 004). Intravenous FADR injection effectively lowered the mRNA expressions of PCNA in breast tumors, which were not apparently altered after local LADR injection. Conclusion: Local injection of LADR holds a strong inhibitory effect on the proliferation of metastatic tumor cells in lymph nodes and appears to be an effective method for the treatment of lymphatic metastases of breast cancer.

Local administration of liposomal adriamycin inhibited proliferation of metastatic cells in axillary lymph nodes in rabbit breast cancer model

Objective： To assess the inhibitory effects of liposomal adriamycin （LADR） locally injected into mammary glands of VX2 tumor-bearing rabbits on proliferation of lymph nodal metastatic cells. Methods： Twenty-one VX2 tumor-bearing rabbits were randomly and equally divided into 3 groups. Rabbits were randomized to receive sham treatment （Group I）, subcutaneous LADR around tumor （Group Ⅱ） and intravenous free adriamycin （Group Ⅲ）, respectively. Breast tumor and axillary lymph nodes were harvested after 3 repeated treatment. Nodal sizes of both pre-and post-treatment were measured. Proliferating cell nuclear antigen （PCNA） mRNA in both tumor and lymph nodes were determined by RT-PCR. Results： The mean size of axillary lymph nodes in Group I, Ⅱ and Ⅲ increased by 3.70%, 1.55% and 2.89%, respectively, with significant difference between Group Ⅲ and I （P=-0.004） and between Group Ⅱ and Ⅲ（P=-0.002）. Relative expression values of PCNA mRNA in breast tumors of Group I, Ⅱ and Ⅲ were 0.486, 0.513 and 0.396, respectively. For Group Ⅲ, PCNA mRNA was significantly less expressed than that in Group I （P=-0.023） and Ⅱ（P=0.005）. Relative expression values of PCNA mRNA in axillary lymph nodes of Group I, Ⅱ and Ⅲ were 0.541, 0.329 and 0.450, respectively. Compared with Group I, Group Ⅲ showed a markedly decreased expression of PCNA （P=-0.021）. The least level ofPCNA mRNA was found in Group Ⅱ, with a significant difference from that in Group Ⅲ（P=-0.004）. Conclusion： Local injection of LADR was an effective therapeutic regimen for lymphatic metastases from breast cancer, regardless of its little effect on primary tumor.