Abstract
Certain non-steroidal anti-inflammatory drugs may possess anti-tumorigenic effects in certain cancer cell types. Sinomenine (SIN) is an alkaloid from Sinomenium acutum, a Chinese medicinal plant that inhibits inflammatory reactions and that has been used in the treatment of neuralgia and rheumatic diseases. In this study, we investigated the anticancer effects of SIN against colorectal cancer in vitro and in vivo, as well as the underlying mechanisms. The effects of SIN on proliferation, cell cycle progression and cyclooxygenase (COX)-2 expression were examined in human colorectal cancer-derived SW1116 cells. The in vivo effects of SIN were examined in a model of SW1116 tumor xenograft growth in athymic nude mice. Changes in COX-2 expression induced by the biological effects of SIN were analyzed by western blot analysis. The effects of SIN treatment on G1 phase cell cycle regulators in xenografts were analyzed by immunohistochemistry. Our findings demonstrate that SIN inhibits the proliferation of SW1116 cells by promoting their accumulation in the G1 phase, with concomitant suppression of COX-2 expression. Time- and dose-dependent inhibition of tumor growth and reduced toxicity were observed in nude mice administered daily intraperitoneal injections of SIN at doses of 25, 50 and 100 mg/kg. SIN-treated tumors also exhibited reduced COX-2 expression, a marked increase in Cip1/p21 protein levels and a decrease in the levels of cyclin D1 and cyclin E. SIN may be an effective chemopreventive agent against colorectal cancer. The growth inhibitory properties of SIN against colorectal cancer may be mediated via a COX-2 inhibitory effect and cell cycle arrest in the G1 phase.