四环素衍生物CMT-8对人类宫颈癌细胞HeLa的生长及其放射敏感性的影响

Anticancer activity and radiosensitization of CMT-8 in human cervical cancer HeLa cells

探讨四环素衍生物CMT-8对人宫颈癌细胞HeLa的生长以及放射增敏性的影响。分别采用MTT法、伤口愈合实验、细胞粘附实验、流式细胞术和Western blot法测定CMT-8对HeLa细胞生长、迁移、粘附、周期的影响及其相关蛋白表达水平的改变。实验结果表明,CMT-8可有效抑制HeLa细胞的生长,降低其迁移、粘附能力,引起细胞G0/G1期阻滞、下调周期蛋白Cyclin D和Cyclin E的表达水平。CMT-8联合X射线能明显抑制细胞的生长,下调DNA损伤修复蛋白Ku70和DNA-PKcs的表达水平。这些发现提示,CMT-8作为人宫颈癌抗肿瘤新药可能是与其抑制细胞生长、细胞周期调控和抗迁移有关。另外,CMT-8在低剂量下可以提高人宫颈癌细胞的放射敏感性,与其调节DNA损伤修复蛋白的表达水平有关。

To investigate the effects of chemically modified tetracycline 8（CMT-8） on cell growth,migration and radio-senstivity in human cervical cancer HeLa cells,MTT assay was used to determine cell viability and radiosensitivity;wound healing and adhesive assays were used to measure cell migration and adhesion;flow cytometry and Western blot assay were performed to analyze cell cycle alteration and protein expression.The results showed that CMT-8 inhibited HeLa cell growth,migration and adhesion in a dose-and time dependent fashion.Furthermore,CMT-8 caused a G0/G1 arrest,in accompany with a dose-dependent down-regulation of Cyclin D and Cyclin E protein expression.Finally,HeLa cells pre-treated with CMT-8 at non-cytotoxic concentrations became more sensitive to subsequent irradiation of X-rays,which was related to a decreased expression of Ku70 and DNA-PKcs protein.Taken together,these findings indicate that CMT-8 is a new anti-cervical cancer compound via inhibiting cell growth and migration as well as mediating radio-sensitivity.