Milk-derived Hexapeptide(LfcinB 4-9) Promotes DDP To Inhibit The Colony And Metastasis Of Human Ovarian Cancer Cells And Its Molecular Mechanism

Objective: To study lactoferrin hexapeptide(Lfcin B 4-9)to reduce the drug resistance of human ovarian cancer cells,and DDP combined with Lfcin B4-9 drugs to human ovarian cancer cells SKOV3,SKOV3/DDP,CI3 K,CI3K/DDP migration and invasion capabilities,and explore its possible mechanism.Methods: MTT was used to detect the proliferation inhibition of DDP combined with Lfcin B4-9 in human ovarian cancer cells SKOV3,SKOV3/DDP,CI3 K,CI3K/DDP;scratch test to detect DDP combined with Lfcin B4-9 medication on human ovarian cancer Cell migration ability;The morphologic changes of human ovarian cells were detected by HE staining and section assay;The effect of DDP combined with Lfcin B4-9 on the clone formation ability of human ovarian cancer cells was detected by plate cloning assay;Transwell assay was used to detect the effect of DDP combined with Lfcin B4-9 on the invasion ability of human ovarian cancer cells;q RT-PCR was used to detect the expression of HSF1,HSP70,OPTN,MDR1,NM23-H1,MTA1,STAT3 、p-STAT3 and other genes in human ovarian cancer cells treated with Lfcin B4-9 and DDP.Western Blot was used to detect the protein expression of HSF1,HSP70,OPTN,MDR1,NM23-H1,MTA1,STAT3 、pSTAT3 and other genes in human ovarian cancer cells under the combined treatment of Lfcin B4-9 and DDP.Results: The results showed that the combined effect of Lfcin B4-9 and DDP had a significantly higher inhibition rate on ovarian cancer cells than the DDP alone group(P<0.05 or P<0.01).The cell morphology of human ovarian cells changed significantly after DDP combined with Lfcin B4-9.Greater than DDP alone group,compared with DDP alone group,after DDP combined with Lfcin B4-9,human ovarian cancer cell clone formation ability and invasion ability were significantly reduced(P<0.05 or P<0.01).The q RT-PCR experiment showed that the expression of HSF1,HSP70,MDR1 and other resistance-related genes when DDP combined with Lfcin B4-9 was significantly lower than that of the control group and DDP alone group,and the expression of OPTN and NM23-H1 was significantly higher than that of the control group and DDP alone group.Western Blot results showed that when DDP combined with Lfcin B4-9,the expression of MTA1,STAT3、p-STAT3 and other migration-related genes were significantly lower than those of the control group and DDP alone group,and the expressions of OPTN and NM23-H1 were significantly higher than those of the control group and DDP alone groupConclusion: The combined effect of Lfcin B4-9 and DDP significantly enhances the sensitivity of ovarian cancer cells to DDP.Its effect is to reduce the expression of resistance-related genes such as HSF1,HSP70,MDR1,etc.,through the signal pathway of HSF1-HSP70-resistant protein At the same time,the combined effect of Lfcin B4-9and DDP also plays a significant role in the migration and invasion-related genes such as MTA1,STAT3,p-STAT3,NM23-H1,and reduces the invasion and migration ability of human ovarian cancer cell lines.