title: Cisplatin-induced senescence and growth inhibition in human non-small cell lung cancer cells with ectopic transfer of p16INK4a.
abstract: 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.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan, Republic of China. biofv033@scc.ntnu.edu.tw
authors.forename: Kang
authors.initials: K
authors.lastname: Fang
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chiu
authors.forename: Chin-Hsiao
authors.initials: CH
authors.lastname: Li
authors.forename: Yung-ta
authors.initials: YT
authors.lastname: Chang
authors.forename: Hwei-tein
authors.initials: HT
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D019942:Genes, p16; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin