Effect Of Lycorine On Apoptosis Of Colon Cancer Cell Line HT29 And Underlying Mechanisms

Background: Cancer is one of the major public health problems in the world.Colorectal Cancer is one of the most common malignant tumors in the world.Colorectal cancer is expected to rank third in all cancers in the United States in 2018,which poses a serious threat to human health.Drug chemotherapy is one of the main methods to treat colorectal cancer.However,the poor selectivity of traditional chemotherapeutic drugs,accompanied by varying degrees of toxicity and side effects,and drug resistance caused by long-term use directly or indirectly affect the prognosis and quality of life of patients.However,many patients have good tolerance to natural compounds,even at high doses,they will not produce obvious toxic and side effects.Therefore,it is urgent to find a more effective natural compound combined with traditionalchemotherapeutic drugs,so as to improve the prognosis and quality of life of patients with colorectal cancer.Objective:(1)To investigate whether Lycorine can inhibit the proliferation and induce apoptosis of colon cancer HT29 cell line.(2)To explore the possible mechanism of Lycorine-induced apoptosis in colon cancer HT29 cell line.Methods:(1)The effect of Lycorine on proliferation and apoptosis of colon cancer HT29 cells was studied.(1)MTT assay was used to detect the effect of Lycorine on proliferation of HT29 cells.(2)Cell cloning assay was used to detect the effect of Lycorine on colony formation of HT29 cells.(3)Hochest33258 was used to observe the effect of Lycorine on apoptotic morphology of HT29 cells.(4)Flow cytometry was used to detect the effect of Lycorine on apoptosis of HT29 cells.(2)Possible mechanism of Lycorine-induced apoptosis in colon cancer HT29 cells.Western blot was used to detect the effects of lycorine on the expression of Bcl-2,Bax,caspase-3,ERK,p-ERK,p38,p-p38,JNK,AKT and NF-?B in HT29 cells.Results:(1)Lycorine could inhibit the proliferation and apoptosis of colon cancer HT29 cells.(1)MTT assay showed that Lycorine could effectively inhibit the proliferation of colon cancer HT29 cells in a time-and concentration-dependent manner(P < 0.05),(2)Cell cloning experiment showed that Lycorine could significantly inhibit the colonyformation ability of HT29 cells which was concentration-dependent(P <0.05).(3)Hochest33258 showed that Lycorine could promote apoptosis of HT29 cells,and the cell morphology showed obvious apoptotic changes.(4)Flow cytometry showed that Lycorine could effectively promote apoptosis of HT29 cells in a concentration-dependent manner(P < 0.05).(2)Western blot results showed that Lycorine could significantly down-regulate the expression of Bcl-2,p-ERK,AKT and NF-?B in HT29 cells,and up-regulate the expression of Bax,caspase-3,p38 and JNK.Conclusion:(1)Lycorine can significantly inhibit the proliferation and induce apoptosis of colon cancer HT29 cell line.(2)Lycorine induces apoptosis in colon cancer HT29 cells,which may be related to the up-regulation of apoptotic protein Bax,caspase-3,down-regulation of apoptotic protein Bcl2 and exogenous apoptotic pathway.(3)The possible mechanism of Lycorine-induced apoptosis in colon cancer HT29 cell line is related to inhibition of MAPK/ERK pathway and activation of MAPK/p38 and MAPK/JNK pathway.(4)The possible mechanism of Lycorine-induced apoptosis in colon cancer HT29 cell line is to inhibit AKT/ NF-?B pathway.