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.