Study On The Mechanism Of Quercetin Inducing Programmed Necrosis Of Tumor Cells

OBJECTIVE: Despite the HPV vaccine and early screening for cervical cancer,cervical cancer remains one of the leading causes of death for all cancers in women between the ages of 20 and 39.Cervical cancer cells tend to gain resistance to common cancer treatments through various mechanisms,so it is necessary to study and find new drugs to overcome the potential of tumor resistance so as to avoid apoptotic resistance of tumor cells.Quercetin(Que),a flavonoid widely found in plants,is the main antioxidant in common Chinese herbs.Quercetin has been found to inhibit many types of cancer and has high potential in cancer treatment,but its anti-tumor mechanism needs further study.The purpose of this study was to investigate the anti-tumor activity of Que in vitro and its mechanism of inducing He La cell death in human cervical cancer.METHODS: 1.Study on the anti-tumor activity of quercetin in vitro MTT assay was used to detect the inhibitory effect of quercetin on tumor cell proliferation.A scratch test was used to detect the proliferation and migration of human cervical cancer He La cells.2.Study on the effect of quercetin on He La cell death in human cervical cancer The activity of LDH in cell culture supernatant was detected by colorimetric method.Hoechst 33342/PI double staining was used to detect the morphological changes of cells treated with quercetin.3.Quercetin induces He La cell necroptosis in human cervical cancer Western Blot was used to detect the expression of the key protein(RIPK1/RIPK3)that quercetin induces necroptosis in He La cells.Effect of the necroptosis inhibitor NEC-1 on the anti-proliferation effect of quercetin.RESULTS: 1.Quercetin inhibits proliferation of He La(cervical cancer),7721(liver cancer),A549(lung cancer),Hep G2(liver cancer),231+(breast cancer)and other tumor cell lines,especially He La cells of human cervical cancer.The scratch test showed that quercetin significantly inhibited the proliferation and migration of He La cells compared with the control group.2.After quercetin treatment,LDH activity in the supernatant of cell culture was increased,and the number of Hoechst 33342/PI double-staining positive cells increased.3.Western blot showed that quercetin could up-regulate the expression of the protein RIPK1/RIPK3 associated with necroptosis in He La cells.CONCLUSION: 1.Quercetin can inhibit human cervical cancer He La cell proliferation in vitro.2.Quercetin can induce He La necroptosis in human cervical cancer,and its mechanism is related to upregulated RIPK1 and RIPK3 proteins.