Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines

Abstract

Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI-N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0.07 mg colchicine/kg/d for in vivo tests). Our results showed that colchicine had the same inhibitory effects on the proliferation of both cell lines. The antiproliferative effects of colchicine on both cell lines were achieved only at the concentration of 6 ng/mL (p < 0.0001). In both cell lines, 18 genes were consistently upregulated and 10 genes were consistently downregulated by 6 ng/mL colchicine, compared with 2 ng/mL colchicine. Among these genes, only the upregulated DUSP1 gene may contribute to the antiproliferative effects of colchicine on gastric cancer cells. The nude mice (BALB/c-nu) experiment showed that colchicine-treated mice after 14 days of treatment had lower increased tumor volume ratios (p = 0.0199) and tumor growth rates (p = 0.024) than the control mice. In conclusion, colchicine has potential for the palliative treatment of gastric cancer. However, the anticancer effects are achieved only at high clinically acceptable colchicine concentrations. Monitoring the colchicine plasma concentration is mandatory if this drug is applied for the palliative treatment of gastric cancer.

Keywords: Animal study; Colchicine; Gastric cancer; Proliferation.

Figure 1

Antiproliferative effects of colchicine on two gastric cancer cell lines—AGS and NCI‐N87. The premixed WST‐1 cell proliferation reagent was applied for investigation. The absorbance is measured at the 450‐nm wavelength (reference wavelength, 630 nm). In all experiments, 16 replicate wells were used to determine the mean and the standard deviation. The unpaired two‐tailed t test was applied for statistical analysis. Bars indicate the standard deviation (SD). (a) p = 0.5052; (b,c,e,f) p< 0.0001; and (d) p = 0.0628. The inhibitory effects of 6 ng/mL colchicine on cellular proliferation are 47.8% and 61.1% for the AGS cells and NCI‐N87 cells, respectively.

Figure 2

Increased tumor volume ratios in the colchicine‐treated mice and the control mice. The increased tumor volume ratio is V_x/V₀ (in which V_x is the tumor volume at day × and V₀ is the baseline pretreatment tumor volume). Data are expressed as the mean value ± standard error of the mean (i.e., error bars). The increased tumor volume ratios in colchicine‐treated mice after 14 days of treatment are significantly lower than in the control mice. (a) p = 0.0199, based on the unpaired t test.