J Cancer 2015; 6(12):1337-1345. doi:10.7150/jca.13054
Knockdown of hTERT and Treatment with BIBR1532 Inhibit Cell Proliferation and Invasion in Endometrial Cancer Cells
1. Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University. Beijing, P. R. China.
2. Division of Gynecological Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
Kong W, Lv N, Wysham WZ, Roque DR, Zhang T, Jiao S, Song D, Chen J, Bae-Jump VL, Zhou C. Knockdown of hTERT and Treatment with BIBR1532 Inhibit Cell Proliferation and Invasion in Endometrial Cancer Cells. J Cancer 2015; 6(12):1337-1345. doi:10.7150/jca.13054. Available from http://www.jcancer.org/v06p1337.htm
Telomerase activity and expression of the catalytic protein hTERT are associated with cell proliferation and advanced stage in endometrial cancer. Our objective was to evaluate the effect of inhibition of hTERT by siRNA and BIBR1532 on cell growth, apoptosis and invasion in endometrial cancer cells. Knockdown of hTERT or treatment of the cells with BIBR1532 decreased telomerase activity, inhibited cell proliferation, induced apoptosis, and reduced cell invasion in Ishikawa and ECC-1 cells. Either hTERT siRNA or BIBR1532 in combination with paclitaxel promoted a synergistic inhibitory effect on cell growth through induction of Annexin V expression and a remarkable reduction in cell invasion through reduction of protein expression of MMP9, MMP2, and MMP3. Increased telomerase activity and hTERT protein expression by transfections enhanced the protein expression of MMPs and increased the cell invasion ability. BIBR1532 significantly antagonized cell invasion induced by increased hTERT expression. These findings suggest that telomerase and hTERT facilitate cell invasion via MMP family in human endometrial cancer cells.
Keywords: telomerase, hTERT, endometrial cancer, apoptosis, paclitaxel.