Abstract
We tested antitumoral activity of vinorelbine, a semisynthetic vinca alkaloid anticancer agent, against human breast carcinoma, in vivo and in vitro. The MCF-7 and R-27 tumors were positive for estrogen receptors and serially transplanted in female nude mice. The maximum tolerated dose of 16 mg/kg vinorelbine was administered intravenously to nude mice after a subcutaneously inoculated tumor started exponential growth. The treated/control (T/C) ratio of relative mean tumor weight was 26.7% for MCF-7 and 44.1% for R-27, showing that vinorelbine was equivalent or superior to other agents commonly used to treat breast cancer. An in vitro study using succinate dehydrogenase inhibition (SDI) showed that the 50% inhibitory concentration (IC50) of vinorelbine was 2.4μg/mL for MCF-7 and 3.0μg/mL for R-27, much lower than for other vinca alkaloids, vindesin or vincristine. The combination chemotherapy experiment using SDI showed that adding 0.01μg/mL of vinorelbine greatly enhanced antitumor activity of 5-fluorouracil (5-FU), suggesting drug synergy. Vinorelbine thus appears to be a powerful second-or third line chemotherapy agent for patients with advanced or metastatic breast cancer.
