17β-Oestradiol activates proteolysis and increases invasion through phosphatidylinositol 3-kinase pathway in human cervical cancer cells

Abstract

Objective: Despite evidence that oestrogen may play an important role in the carcinogenesis of cervical cancer, its action and mechanism in cervical cancer invasion are not well defined.

Study design: The invasion induced by 17β-oestradiol (E2) was measured by invasion assay. Real-time polymerase chain reaction (PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and gelatin zymography were used to study the role of E2 on metastasis-related proteases. The signal pathway was also investigated.

Results: E2 was found to significantly enhance the invasion of cervical cell lines including HeLa, CaSki and SiHa cells, but not C33A cells. Moreover, E2 10(-8)M increased the expression and activation of matrix metalloproteinases (MMP-2 and MMP-9) in HeLa and CaSki cells, as shown by real-time PCR, Western blot, ELISA and gelatin zymography. The expression of tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) was decreased significantly by E2. Pretreatment with GM6001 10 μM (total MMP inhibitor) or SB-3CT 20 μM (specific gelatinase inhibitor) blocked the pro-invasive effect of E2. E2 was found to induce invasion via the phosphatidylinositol 3-kinase (PI3K) signalling pathway.

Conclusion: E2 may contribute to cervical cancer metastasis through activation of proteolysis and increased invasion via the PI3K pathway.