Fang Kang, Chiu Chien-Chih, Li Chin-Hsiao, Chang Yung-ta, Hwang Hwei-tein
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan, Republic of China.
Oncol Res. 2007;16(10):479-88. doi: 10.3727/096504007783338331.
DNA damage is lethal and capable of inducing cellular aging or apoptosis. In this work, the highly tumorigenic and cisplatin-resistant human non-small cell lung cancer (NSCLC) cells were transfected with construct encoding the complete sequence of p16INK4a (p16). The stable clones with elevated p16 exhibited enhanced sensitivities to low concentration cisplatin treatment. Further study indicated that cisplatin arrested cells at G2/M phase and the effectiveness is proportional to the level of p16 expressed. The growth of the xenograft tumors established by p16 transfectants in nude mice was also suppressed by cisplatin by inducing senescence-like phenotype. The data altogether indicated that, in cisplatin-resistant tumor cells with basal endogenous p16, the growth suppression by drugs can be greatly improved by ectopic gene transfer.
DNA损伤是致死性的，能够诱导细胞衰老或凋亡。在本研究中，将编码p16INK4a（p16）完整序列的构建体转染至具有高度致瘤性和顺铂抗性的人非小细胞肺癌（NSCLC）细胞中。p16表达升高的稳定克隆对低浓度顺铂治疗表现出更高的敏感性。进一步研究表明，顺铂使细胞停滞于G2/M期，其有效性与p16的表达水平成正比。顺铂通过诱导衰老样表型，也抑制了p16转染体在裸鼠中形成的异种移植肿瘤的生长。这些数据共同表明，在具有基础内源性p16的顺铂抗性肿瘤细胞中，通过异位基因转移可大大提高药物对生长的抑制作用。
