Abstract
It is reported that sinomenine (SIN) and 5-fluorouracil (5-FU) both are effective for colon cancer, but their cooperative suppressive effects and toxicity remain to be clarified in detail. This study aimed to determine suppressive effects and toxicity of sinomenine (SIN) plus 5-fluorouracil (5-FU) on LoVo colon carcinoma cells in vitro and in vivo. CCK-8, Hoechst 33258 staining and an annexin V-FITC/PI apoptosis kit were used to detect suppressive effects. Western blotting was applied to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis. SIN or 5-FU or both were injected into nude mice, and then suppressive effects and side effects were observed. SIN plus 5-FU apparently inhibited the proliferation of LoVo cells and induced apoptosis. Moreover the united effects were stronger than individually (p<0.05). The results of annexin V-FITC /PI staining and Hoechst 33258 staining showed that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone was significantly higher than the control group (p<0.05). Expression of Bax and Bcl-2 was up-regulated and down-regulated respectively. SIN or 5-FU significantly inhibited effects on the volume of tumour xenografts and their combined suppressive effects were stronger (p<0.05). No obvious side effects were observed. It was apparent that the united effects of SIN and 5-FU on the growth of colorectal carcinoma LoVo cells in vitro and in vivo were superior to those using them individually, and it did not markedly increase the side effects of chemotherapy.
Highlights
Colorectal cancer is the fourth most common cancer in the world, and significant international variations in the distribution of colorectal cancer have been observed (Center et al, 2009; Siegal et al, 2013)
It is reported that sinomenine (SIN) and 5-fluorouracil (5-FU) both are effective for colon cancer, but their cooperative suppressive effects and toxicity remain to be clarified in detail
Apoptosis induced by SIN or 5-FU As time goes on during the 48 hours of incubating, the proportion of Annexin V-positive/Propidium Iodide (PI)-negative cells were gradually increasing in the LoVo cells incubated at low concentrations of SIN (200 μM) and 5-FU (50 μM)
Summary
Colorectal cancer is the fourth most common cancer in the world, and significant international variations in the distribution of colorectal cancer have been observed (Center et al, 2009; Siegal et al, 2013). The main therapy on primary colon carcinoma is surgical resection, but only half of them can be cured with the rest hopeless. For better prognosis after surgical resection or other clinical situations, chemotherapy as a relatively effective therapy is used more and more. Whereas the uncontrollable toxicity and dissatisfying effective rate which around 20-35% with median overall survival no more than 1 year could not meet the needs of treatment (Wu et al, 2013; Focan et al, 2013; Ghiringhelli et al, 2013). To seek a way such as united therapy that can improve the effective rate and decrease toxicity of 5-FU on colon carcinoma is very important. The combination of a natural, low-toxicity and highefficacy agents with 5-FU may be better
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