| High fatality rate is one of the properties of ovarian cancer, since it lacks specific physical symptom, and it's hard to make a diagnosis at the initial stage. About 70% of patients with ovarian cancer are diagnosed at advantage stage and have metastasis simultaneously. Surgery and chemotherapy are still the main methods to cure ovarian cancer in clinical treatment. However, those patients at advantage stage and have metastasis simultaneously, are not appropriate for surgery. Even if the patients have been made by surgical therapy, recurrence or metastasis of this kind of cancer are possible. So, it is key to find out metastasis promoting targets and prevent/intervene ovarian cancer metastasis for clinical cure. In this study, the mechanisms of IL-8 promoting ovarian tumor cells migration and the inhibity effects of TMP on ovarian tumor cell migration were detected.Part one: The mechanisms of exogenous IL-8 promoting human ovarian tumor cells migrationTo detect the effect of exogenous IL-8 on ovarian cancer cell migration, Transwell assay was uesed to underlie IL-8 has the ability to promote ovarian cancer cells migration. Then, the protein levels of E-cadherin in SKOV-3 and OVCAR-3 were down-regulated. However, total protein levels ofβ-catenin in SKOV-3 and OVCAR-3 were up-regulated followed by IL-8 (100ng/ml) treatment. Meanwhile, the phosphorylation levels ofβ-catenin in cytoplasm and in nucleus were inhanced respectively and significantly. A further investigation showed that the protein levels of OGT were down-regulated by IL-8 in SKOV-3 and OVCAR-3;Otherwise,it has been demonstrated that the protein level of O-GlcNAC were suppressed by IL-8 in ovarian tumor cells. The band with a molecular mass of approximately 95KD in western blot assay, is similar toβ-catenin (92-95KD). These data suggested that exogenous IL-8 induced human ovarian cancer cell migration might be related to suppression of E-cadherin protein expression and the changes in the expression and structure ofβ-catenin.Part two: The effects of TMP on cell migrationInterleukin-8 (IL-8) expression by melanoma cells could influence their metastatic capabilities. Tetramethylpyrazine (TMP) from Ligusticum wallichil franchat possess characteristics of anti-inflammation and antitumor. It has recently been suggested that autocrine IL-8 may play a role in tumor cell survival, invasion, and migration. The role of TMP related with IL-8 in tumor cell migratory process remains unclear. The purpose of the present study was to determine whether TMP can influence migration of human ovarian carcinoma cell line (SKOV-3) via regulating IL-8 expression in vitro. Cell counts showed that treatment of SKOV-3 with TMP (25-100μg/ml) for 24 h did not decrease the cell number, while effect of TMP on the down-regulation expression of IL-8 was observed. In addition, migration of SKOV-3 cells was suppressed after treatment with TMP (25-100μg/ml) for 24 h. So, expression of IL-8 by SKOV-3 cells correlates with their metastatic potential. Western blot analysis revealed that ERK1/2 and p38 phosphorylation was blocked by TMP. Furthermore, IL-8 mRNA expression was inhibited significantly after co-incubation with PD98059 (ERK inhibitor) and SB203580 (p38 inhibitor), respectively. Interestingly, these changes were observed as to activator protein-1 (AP-1) activity suppression rather than that of NF-κB. Our data suggests that TMP may inhibit tumor cell invasion and migration, at least in part, through its activity of down-regulation IL-8 expression. Our results provided evidence that anti-inflammation plays an important role in integrative cancer therapies.
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