Inhibitory effect and mechanism of vitexin on the growth of transplanted nasopharyngeal carcinoma CNE-2 cells in nude mice based on AMPK/ULK1 mediated autophagy
Objective To investigate the inhibitory effect of vitexin on the growth of nasopharyngeal carcinoma CNE-2 cells transplanted into nude mice and its possible regulatory mechanism.Methods BALB/c nude mice were inoculated with CNE-2 cells under the left forearm armpit to construct a nasopharyngeal carcinoma nude mice tumor model.After the model was successfully constructed,they were randomly divided into model group,vitexin group(5 and 10 mg/kg),AMPK agonist group(AICAR,200 mg/kg),and vitexin + AMPK inhibitor group(Compound C,20 mg/kg),with 10 mice in each group.Vitexin group was ig administered at corresponding doses,AICAR group received ip injection of 200 mg/kg AICAR,vitexin + Compound C group received 10 mg/kg vitexin by ig and ip injection of 20 mg/kg Compound C,and the above groups were continuously administered for 21 d.Measure the volume and mass of transplanted tumor in nude mice after administration.HE staining was used to observe the pathological changes of the transplanted tumor tissue,TUNEL staining was used to detect apoptosis in tumor tissue.Detection of LC3-Ⅱ and p62 protein expression by immunohistochemical in tumor tissue,immunofluorescence detection of LC3-Ⅱ and Caspase-3 expression in tumor tissue,Western blotting was used to detect the relative expression of Bax,Bcl-2,Casapse-3 proteins,and AMPK/ULK1 pathway related proteins in tumor tissue.Results Compared with the model group,the tumor growth was slow,tumor volume and mass were significantly reduced(P<0.05),tumor cell apoptosis rate,the protein expression of Caspase-3,LC3-Ⅱ,Bax/Bcl-2,p-AMPK/AMPK,p-ULK1/ULK1 were significantly increased,and p62 protein expression were significantly reduced(P<0.05)in each dose group of vitexin.Compared with the 10 mg/kg group of vitexin,the vitexin + Compound C group showed good tumor growth,increased tumor volume and mass(P<0.05),increased tumor cell apoptosis rate,the protein expression of Caspase-3,LC3-Ⅱ,Bax/Bcl-2,p-AMPK/AMPK,p-ULK1/ULK1 were significantly decreased,while p62 protein expression were significantly increased(P<0.05).Conclusion Vitexin can inhibit the growth of nasopharyngeal carcinoma CNE-2 cells transplanted into nude mice,and its mechanism is related to activating AMPK/ULK1 pathway mediated autophagy and promoting tumor cell apoptosis.
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