ROMIDEPSIN AFFECTS THE GROWTH, PROLIFERATION, AND APOPTOSIS OF COLON CANCER CELLS THROUGH ACTIVATING AKT/ERK/NF-ΚB PATHWAY

Shuang Xie^#, Quanhui Wang^#, Shouxin Yuan, Zhuyin Wu, Jixin Zhang, Yuanhao Zhang, Chunxu Zhang^* 

Department of General Surgery, The 988th Hospital of PLA Joint Logistics Support Force, Zhengzhou 450003, PR China

Objective: This study investigates the effect of romidepsin on the growth, proliferation and apoptosis of colon cancer cells by activating the AKT/ERK/NF-κB pathway. 

Methods: Human colon cancer cell lines were cultured in vitro to establish a mouse subcutaneous xenograft tumour model. When the tumours reached approximately 10 mm, the mice were randomly divided into a saline group and a romidepsin group (10 mg/kg), and the tumour size of the two groups were measured. Human colon cancer cell lines were treated with 1, 5 and 10 mg/L romidepsin. The proliferation of colon cancer cells was detected by CCK-8, the apoptosis by flow cytometry, and the phosphorylation levels of protein kinase B (AKT), externally regulated protein kinase (ERK) and nuclear transcription factor-κB (NF-κB) proteins by a western blot. 

Results: T26 cells were inoculated subcutaneously into the backs of mice. The tumour size was measured after its formation. It was noted that, compared with the saline group, the growth of colon cancer in mice was significantly inhibited in the romidepsin group (10 mg/L). In addition, compared with the control group, the proliferation rate was not significantly restrained in the romidepsin group (1 mg/L) (P>0.05) but greatly inhibited in the romidepsin group (5 and 10 mg/L), which was time- and dose-dependent (P<0.05). After being treated with 1 mg/L, 5 mg/L and 10 mg/L romidepsin, the apoptosis rate of colon cancer cells gradually increased, and with the increase of drug concentration, the percentage of apoptosis elevated from the normal 5.42%±0.15% to 41.83 %±2.79% (P<0.05). The expression levels of p-AKT, p-ERK and p-NF-κB in colon cancer cells treated with 10 mg/L romidepsin were significantly lower than those in the control group. 

Conclusions: Romidepsin can inhibit the growth and proliferation of colon cancer cells but can promote their apoptosis. The related mechanism may be achieved by regulating the AKT/ERK/NF-κB signalling pathway.