Anticancer effects of 5-fluorouracil combined with warming and relieving cold phlegm formula on human breast cancer

Abstract

To investigate the anticancer effects of warming and relieving cold phlegm formula (, WRCP), a Chinese medical mixture composed of the aqueous extracts of Aconitum carmichaeli, Rhizoma bolbostemmatis, Phytolacca acinosa, Panax notoginseng, and Gekko swinhonis Gūenther, combined with 5-fluorouracil (5-FU) on human breast cancer in vivo. Seventy-two Nu/Nu mice inoculated with MDA-MB-231 breast cancer cells were randomized into the control group, 5-FU group, high-dose WRCP (hWRCP) group, medium-dose WRCP (mWRCP) group, low-dose WRCP (lWRCP) group, or combination of mWRCP and 5-FU group in a 1:1:1:1:1:1 ratio. Drug administration was commenced on the day following tumor implantation. The control group was injected daily with normal saline (N.S.) intraperitoneally; the 5-FU group was injected with 5-FU at 30 mg/kg intraperitoneally every third day for a total of 7 treatments; the hWRCP group, mWRCP group and lWRCP group received daily doses of 5, 1, and 0.2 g/kg of WRCP, respectively, by gastric perfusion; and the combination group was treated with 5-FU plus mWRCP on the same schedules as above. All treatments lasted for 22 days. Tumor volume, tumor weight, inhibition rate of tumor weight, necrosis rate of tumor, organ index, and change in body weight of nude mice were measured. The combination group and the hWRCP group had significantly smaller tumor volumes (580±339 mm(3) and 587±249 mm(3) versus 1055±234 mm(3), respectively), lower tumor weights (0.42±0.29 g and 0.52±0.29 g versus 0.80±0.15 g, respectively), and higher tumor necrosis rates (22.7% and 25.6% versus 9.4%, respectively) as compared with the control group (all <0.05). Similar changes were found in the 5-FU, mWRCP, and lWRCP groups when compared with the control group but were not statistically significant, except for the tumor weight for the 5-FU group. The combination group and the hWRCP group had significantly smaller tumor volumes compared with the 5-FU group (778±202 mm(3), both <0.05). The combination group had the highest tumor inhibition rate (47.7%), followed by the hWRCP group (35.2%) and 5-FU group (28.3%). The 5-FU group had a lower body weight increase (1.37±2.06 g versus 5.60±0.72 g, <0.05) and a lower spleen index (4.064±1.774 mg/10 g versus 5.294±1.796 mg/10 g) as compared with the control group, whereas the combination group reversed the changes in the 5-FU group with the body weight increase of 3.52±1.80 g (P <0.05) and spleen index of 7.036±1.599 mg/10 g (P <0.05). The spleen indices in the hWRCP, mWRCP, and IWRCP group were all significantly higher than that in the 5-FU group (P <0.01 or P<0.05). No significant differences in body weight change were observed in WRCP groups compared with the control group P>0.05). The treatment combination of WRCP and 5-FU was more effective in the inhibition of tumor growth than either agent alone and may have potentially additional benefit in improving the general condition and immunity of the mice with human breast cancer cell implants.