Abstract：【Objective】 To investigate the role of 5-fluorouracil in promoting apoptosis of HPV positive cervical cancer cells and the signal pathway mechanism of Wnt/β-Catenin . 【Methods】 HPV positive cervical cancer cell SiHa was randomly divided into control group and low dose group (10 μmol/L 5-fluorouracil), high dose group (40 μmol/L 5-fluorouracil) and Wnt inhibitor (ICG-001) group (10μmol/L ICG-001);Except that the control group was given sterile phosphate buffer, the other groups were given corresponding doses of drugs. Proliferation and apoptosis of cells in each group (apoptosis rate and apoptotic proteins Caspase-3 and Caspase9) and the expression level of Wnt/β-catenin signaling pathway related proteins (Wnt/β-catenin ) was compared. 【Results】 5-fluorouracil could significantly inhibit the proliferation of HPV positive cervical cancer cells, increase the rate of apoptosis and the expression of apoptotic proteins Caspase-3 and Caspase-9 (P<0.05);After 5-fluorouracil was treated,the expression of key proteins (Wnt and β-catenin) of Wnt/β-catenin signaling pathway was significantly decreased (P<0.05);With the increase of dose, the above effect is more obvious (P<0.05). 【Conclusion】5-fluorouracil can promote the apoptosis of HPV positive cervical cancer cells, which may be related to its inhibition of Wnt/β-Catenin signaling pathway.
[1] BERRAHO M,AMARTI-RIFFI A,EL-MZIBRI M,et al. HPV and cofactors for invasive cervical cancer in Morocco: a multicentre case-control study[J].BMC Cancer,2017,17(1):435.
[2] LAJER C B,GARNAES E,FRIIS-HANSEN L, et al.The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer[J].Br J Cancer,2017,117(5):e2.
[3] CHEN X X,LAM K H,CHEN Q X,et al. Ficus virens proanthocyanidins induced apoptosis in breast cancer cells concomitantly ameliorated 5-fluorouracil induced intestinal mucositis in rats[J].Food Chem Toxicol,2017,110:49-61.
[4] THYSIADIS S,KATSAMAKAS S,DALEZIS P,et al. Novelc(RGDyK)-based conjugates of POPAM and 5-fluorouracil for integrin-targeted cancer therapy[J].Future Med Chem,2017,9(18):2181-2196.
[5] PENG Y,ZHANG X,MA Q,et al.MiRNA-194 activates the Wnt/beta-catenin signaling pathway in gastric cancer by targeting the negative Wnt regulator,SUFU[J].Cancer Lett,2017,385:117-127.
[6] AREND R C,LONDONO-JOSHI A I,GANGRADE A,et al.Niclosamide and its analogs are potent inhibitors of Wnt/beta-catenin,mTOR and STAT3 signaling in ovarian cancer[J].Oncotarget,2016,7(52):86803-86815.
[7] CHO Y H,CHA P H,KADUWAL S,et al.KY1022,a small molecule destabilizing Ras via targeting the Wnt/beta-catenin pathway,inhibits development of metastatic colorectal cancer[J].Oncotarget,2016,7(49):81727-81740.
[8] GARG B,GIRI B,MAJUMDER K,et al. Modulation of post-translational modifications in beta-catenin and LRP6 inhibits Wnt signaling pathway in pancreatic cancer[J].Cancer Lett,2017,388:64-72.
[9] ZOU Y F,XIE C W,YANG S X,et al. AMPK activators suppress breast cancer cell growth by inhibiting DVL3-facilitated Wnt/beta-catenin signaling pathway activity[J].Mol Med Rep,2017,15(2):899-907.
2022, Vol. 39 
