Effects Of GP-7 On The Metastasis Potential Of Human Tongue Carcinoma Tca-8113 Cells In Vitro

Objective: 4-[4″-(2″, 2″, 6″, 6″-tetramethyl-1″- piperidinyloxy nitroxide radical) amino]-4′-demethyl epipodopHyllotoxin(GP-7) is one of semi-synthesized derivatives of nitroxide-introduced pHyllotoxin, which has lower toxicity and higher activity. It has been reported that GP-7 has significant anti-tumor effects on many kinds of cancer. However, the effects and mechanisms of GP-7 on Tca-8113 cells’ proliferation, invasion, migration and adhesion viabilities have not been reported until now. In the study, we investigated the effects and mechanism of GP-7 on Tca-8113 cells proliferation and metastasis in vitro.Methods: The proliferation viability of Tca-8113 cells treated with GP-7 was measured using Sulforhodamine B(SRB) assay. The viabilities of Tca-8113 cell’s invasion and migration were evaluated by Transwell chamber migration assay. The viability of Tca-8113 cell’s adhesion was assayed by cell-matrix adhesion assay. The protein expression levels were determined by Western blotting analysis. The MMP-2 and MMP-9 levels were determined by Gelatin ZymograpHy assay. The NF-κB P65 nuclear transferation and activation capacity were determined using Nuclear Translocation Assay Kit.Results: The SRB assay showed that GP-7 25μg/m L significantly inhibited Tca-8113 cell proliferation. The inhibition rates of GP-7 in 24 h, 48 h, and 72 h respectively were 67.49%, 70.58%, and 94.40%, respectively. GP-7 25μg/m L obviously inhibited Tca-8113 cell invasion, migration and adhesion in 24 h, respectively and their inhibition rates were 84.89%, 79.16%, 58.69%, respectively. Moreover, the expressions of p-Akt and p-IKK were reduced after treated GP-7 for 24 h. The levels of MMP-2 and MMP-9 were also reduced. Immunohistochemical assay showed that with the increase of the concentration of GP-7, the capacity of p65 entering into the nucleus gradually reduced.Conclusion: GP-7 can inhibit the proliferation, invasion, migration and adhesion viabilities of Tca-8113 cell in vitro. It has the inhibitory potential to Tca8113 cells metastasis. The mechanism may be related to the reduction of p-Akt, p-IKK expressions, nuclear transfer capacity.