Inhibitory Effect of Minocycline on in Vitro Invasion and Experimental Metastasis of Mouse Renal Adenocarcinoma

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Abstract
Degradation of the extracellular matrix by metalloproteinases is a critical phenomenon in cancer invasion and metastasis. Recent studies have revealed that minocycline (minocycline hydrochloride, a tetracycline) suppresses in vivo and in vitro mammalian collagenolytic activity. We investigated whether minocycline inhibited in vitro invasion and experimental pulmonary metastasis in subline-2 of streptozotocin-induced mouse renal adenocarcinoma (MRAC-PM2) cells. In vitro invasion assay demonstrated that treatment with 0.5 microgram/ml or 5.0 micrograms/ml minocycline significantly inhibited the invasion of MRAC-PM2 cells. In addition, intraperitoneal administration of 0.5 mg per mouse minocycline reduced the number of metastatic nodules in the lung when MRAC-PM2 cells were injected intravenously. Minocycline also suppressed type IV collagenolytic activity of the cells. However, the drug did not affect [3H]-thymidine uptake, growth of subcutaneously inoculated cells, attachment to the extracellular matrices, or haptotactic migration of the cells. These results indicated that the inhibitory action of type IV collagen degradation by minocycline can contribute, in part, to suppression of the in vitro invasion and metastatic potential of MRAC-PM2 cells.