| Objective Oldenlandia Diffusa injection effect on colorectal cancer and its mechanism.Method1.Clinical study: We randomly divided the 78 patients with advanced colon cancer into control group and treatment group.The control group received only mFOLFOX6chemotherapy(Oxaliplatin 85 mg/m2 IV over 2 hours,day 1;Leucovorin 400 mg/m2 IV over 2 hours,day 1;5-FU 400 mg/ m2 IV bolus on day 1,then 1200 mg/m2/day* 2 days(total 2400 mg/m2 over 46 hours).The treatment group received Oldenlandia Diffusa injection 4ml in tramuscular injection,2 times a day for 10 days).All treatments in the control group and the treatment group were treated with 2 weeks as a treatment cycle,and after 6 cycles,the short-term clinical efficacy,the improvement of quality of life and the impact on safety indexes were compared between the control group and the treatment group.2.Study in nude mice: xenograft in 48 nude mice using HT-29 cell were constructed and randomly divided into 4 groups of 12 nude mice,respectively.The control group:saline 0.1m L /(10g.d)were given.Low dose group: Oldenlandia Diffusa injection3.75 mg /(kg.d)were given.Medium dose group: Oldenlandia Diffusa injection 7.5mg /(kg.d).High dose group: Oldenlandia Diffusa injection 15 mg /(kg.d).After inoculation of HT-29 colon cancer cells,the nude mice were injected intraperitoneally,the volume of0.1mL/(10g.d)was given,and 14 d was given continuously.The nude mice were killed and the whole tumor tissue was removed immediately after the administration,and the tumorsize and tumor suppressor rate of the control and treatment groups were compared.Immunohistochemical method was used to detect the expression level of NMDAR1 in human colon cancer cell HT-29 xenografts in nude mice.Results1.Clinical study: There was no significant difference between the treatment group and the control group in gender distribution and age composition(P> 0.05).There was significant difference between the control group and the treatment group in clinical efficacy after 6 cycles of treatment(c2 =6.010,P=0.014).The total improvement rate of KPS score in the treatment group was significantly higher than that in the control group(c2 =8.423,P=0.038).In the reverse side of the toxic and side reaction,the renal function was not damaged in all two groups.The reduction of hemoglobin and leukocyte decrease in the treatment group were lower than those in the control group,the difference was statistically significant(P<0.05).However,in thrombocytopenia and liver function damage,the two groups were not statistically significant(P> 0.05).In neurotoxicity,the treatment group was significantly lower than the control group.The difference was statistically significant(c2 = 9.523,P=0.023),but there was no significant difference between the treatment group and the control group in the hand foot skin reaction(c2 = 0.647,P=0.724).2.Study in nude mice: Oldenlandia Diffusa injection in different concentrations inhibited growth of colon cancer xenografts.The inhibition rates of low dose group,middle dose group and high dose group were 46.88%,55.97% and 57.39% respectively.The tumor volume in the control group was significantly higher than that in the low-dose group,medium-dose group and high-dose group(P <0.05).There was significant difference in the inhibition rates between the low-dose group,the middle-dose group and the high-dose group(P <0.05)There was no significant difference between the high dose group and the high dose group(P> 0.05).Expression of NMDAR1 in tumor tissues injecting Oldenlandia Diffusa extract of low,medium and high dose was significantly lower than that in the control group(P <0.05).There was significant difference in the expression of NMDAR1between the low dose group and middle dose group(P <0.05).However,there was no significant difference in the expression of NMDAR1 between the medium-dose group and the high-dose group(P> 0.05).Conclusion1.Oldenlandia Diffusa injection combined with chemotherapy in the treatment of advanced colorectal cancer can improve clinical efficacy,improve KPS of patients,reduce adverse reactions of leucocyte and hemoglobin decreased and neurotoxicity.However,there is no obvious advantage in reducing platelet reduction,reducing liver damage and reducing hand,foot and mouth skin reactions.2.There may be related to the reduction of NMDAR1 which Oldenlandia Diffusa can inhibit the growth of colon cancer xenografts in nude mice.However,Oldenlandia Diffusa no longer inhibit growth of nude mice xenografts and increase NMDAR1 expression after Oldenlandia Diffusa more than the optimal concentration. |
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