[Effect of histamine on metastasis of melanoma B16 cell xenograft in C57BL/6 mice].

BACKGROUND & OBJECTIVE: In the biotherapy for tumors, microvessel permeability is the main barrier for large molecular antibody-coupled antitumor drugs to enter the tumor mass. Histamine may enrich these drugs in the tumor matrix through enhancing microvessel permeability and tissue-fluid formation. This study was to investigate whether the increased microvessel permeability and more tissue fluid formation could increase the probability of lymphatic or hemal metastasis of tumor cells.

METHODS

Cultured melanoma B16 cells were inoculated into the left armpit of C57BL/6 mice to develop melanoma. Five days after inoculation, the test group were injected subcutaneously at the dorsal part with histamine (300 mg/kg) every other day for 5 times, while the control group were given normal saline. The metastasis statuses in the lymph node, liver, lung, spleen, and brain were examined by histochemistry. Student t-test and Fisher's exact test were used respectively to analyze the effects of histamine on tumor growth and metastasis.

RESULTS

All the mice developed melanoma after inoculation. At the end of the experiment, the tumor weight was significantly lighter in test group than in control group [(5.26 +/- 1.55) g vs. (6.96 +/- 1.31) g, P < 0.01]. The lymphatic and hemal metastasis rates were significantly lower in test group than in control group (33.3% vs. 75.0%, P < 0.05; 25.0% vs. 75.0%, P < 0.05).

CONCLUSION

Histamine can inhibit the metastasis of melanoma B16 cells in C57BL/6 mice either through lymphatic or hemal route, and this partly because of its inhibitory effect on tumor growth.