Zhang Ying, Lin Chen, Qian Hai-li, Lang Jing-he, Fu Ming, Zhang Xue-yan, Liang Xiao, Duan Hua, Xiang Yang
Beijing Obstetrics and Gynecologic Hospital, Capital Medical University, Beijing 100006, China.
Zhonghua Zhong Liu Za Zhi. 2007 Jan;29(1):25-9.
To investigate the effects of adenovirus-delivered tissue inhibitor of metalloproteinases-3 ( Ad-TIMP-3) on sensitivity of cervical cancer cells to cisplatin and evaluate the potential application of this combined scheme in cervical cancer treatment.
Cells of cervical cancer CaSKi cell line were infected with Ad-TIMP-3 in vitro. Apoptotic effect, cell cycle changes and p53 protein expression were detected. After combined treatment of those cells with cisplatin, colony formation test was performed and cytotoxicity was detected by MTT. The growth curve and tumor growth inhibition in vivo were evaluated.
The expressions of TIMP-3 mRNA and protein were significantly upregulated after transfection. As a result, massive apoptosis was induced and the cells were arrested at G2/M phase. Exogenous overexpression of TIMP-3 increased p53 protein level markedly in spite of the backgrounds of p53 gene in cells. Combined with cisplatin treatment, the cloning efficiency was decreased. A synergism was observed by isobolic method ( D < 1 ) in vitro and tumor growth was significantly inhibited in vivo.
Ad-TIMP-3 is a powerful proapoptotic agent. It increases sensitivity of the cells to cisplatin and the Ad-TIMP-3 gene therapy in combination with cisplatin could be a promising alternative in cervical cancer treatment.
探讨腺病毒介导的金属蛋白酶组织抑制剂-3（Ad-TIMP-3）对宫颈癌细胞顺铂敏感性的影响，并评估该联合方案在宫颈癌治疗中的潜在应用价值。
体外将Ad-TIMP-3感染宫颈癌CaSKi细胞系，检测细胞凋亡效应、细胞周期变化及p53蛋白表达。将这些细胞与顺铂联合处理后，进行集落形成试验，并用MTT法检测细胞毒性。评估体内生长曲线和肿瘤生长抑制情况。
转染后TIMP-3 mRNA和蛋白表达显著上调，结果诱导了大量细胞凋亡，细胞停滞于G2/M期。尽管细胞中p53基因背景不同，但TIMP-3的外源性过表达显著提高了p53蛋白水平。与顺铂联合处理后，克隆效率降低。体外采用等效线法观察到协同作用（D<1），体内肿瘤生长明显受到抑制。
Ad-TIMP-3是一种强大的促凋亡剂，它增加了细胞对顺铂的敏感性，Ad-TIMP-3基因治疗联合顺铂可能是宫颈癌治疗中一种有前景的替代方案。
