Published online Dec 7, 2013. doi: 10.3748/wjg.v19.i45.8292
Revised: October 4, 2013
Accepted: October 13, 2013
Published online: December 7, 2013
Processing time: 113 Days and 10.3 Hours
AIM: To investigate the inhibitory effects of sinomenine (SIN) combined with 5-fluorouracil (5-FU) on esophageal carcinoma in vitro and in vivo.
METHODS: Esophageal carcinoma (Eca-109) cells were cultured in DMEM. The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8 dye in living cells. Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis. Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN at 25 mg/kg and 5-FU at 12 mg/kg every 3 d, either combined or alone, was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed.
RESULTS: SIN and 5-FU, both in combination and individually, significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis. Furthermore, the combined effects were greater than those of the individual agents (P < 0.05). Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control (P < 0.05). The up-regulation of Bax and down-regulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway. SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo, and the combined inhibition rate was even higher (P < 0.05). During the course of chemotherapy, no obvious side effects were observed in the liver or kidneys.
CONCLUSION: The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds, and the drug combination did not increase the side effects of chemotherapy.
Core tip: The cooperative inhibitory effects of sinomenine (SIN) and 5-fluorouracil (5-FU) on esophageal carcinoma in vitro and in vivo were investigated. SIN and 5-FU alone or in combination significantly inhibited the proliferation and induced apoptosis of esophageal carcinoma cells in a dose-dependent manner. The essential mechanism underlying SIN and 5-FU-induced apoptosis, as investigated by Western blotting, involved the mitochondrial pathway. No obvious side effects were observed in the liver and kidneys of nude mice. These results indicated that the combined effects of SIN and 5-FU on esophageal carcinoma were superior to the effects of the individual compounds, without an increase in side effects.