Studies Of Resveratrol Effects On Cervical Cell Growth, Invasion And Radiosensitization

The Objective of this research is to study the impact of resveratrol on the cell adhesion, growth and invasion as well as radiosenstivity in human cervical cancer cells and the involved mechanisms. The major finding including (1) At higher doses resveratrol delayed cell adhesion and inhibited cell growth in a dose and time dependent manner, as demonstrated by in vitro cell adhesion and MTT cell viability assay; (2) At lower doses, resveratrol reduced cell migration and invasive capability in a dose and time dependent manner, as observed by in vitro scratches assay; (3) Resveratrol caused a G2/M arrest of cell cycle progression without apoptosis induction (no sub-G1 occurrence), as observed by analysis of flow-cytometry; and (4) Cells pre-treated with resveratrol at lower doses became more sensitive toγ-irradiation, which also depended up resveratrol doses.To study the potential mechanism(s) involved in the anti-cell growth, invasion and radiosensitization caused by Resveratrol, target genes were determined by RT-PCR and Western blot assays, showing that (1) Up-regulation and the tumor metastasis gene KAI1 was observed in resveratrol treated cells, at both mRNA and protein levels, while knocking-down KAI1 expression significantly reduced the capability of resveratrol anti-invasion, which suggest that KAI1 is a critical targeting gene in the resveratrol anti-invasion activity; (2) Resveratrol did not influence apoptosis-related gene Bax, Bcl-2和heat shock protein p72/73 level, which is consistent with the data in which no apoptosis induction was observed in the cells treated with resveratrol; (3) Resveratrol significantly reduced the expression of a few DNA damage repair proteins, including ATM, NBS1, DNA ligase IV, DNA-PKcs, Ku70 and Ku80, but caused no alteration of XRCC4,γ-H2AX, p53 and ATR expression. DNA ligase IV down-regulation resulted in a significant reduction of resveratrol-mediated radiosensitivity. These results indicate that an inhibition of DNA damage repair proteins may be an important mechanism contributing the radiosensitization caused by resveratrol.In summary, the present findings suggest, the first time, that resveratrol is a new promising chemotherapeutic agent in therapy of cervical cancer, which either can inhibit the cell adhesion, growth, migration and invasion or increase cell sensitivity toγ-irradiation. These in vitro results will provided a new research direction in controlling cervical cancer cell growth, invasion and metastasis, and pre-clinical experimental basis for resveratrol as a new therapeutic agent in therapy of cervical cancer.