title: The apoptosis of non-small cell lung cancer induced by cisplatin through modulation of STIM1.
abstract: Cis-diamminedichloroplatinum (II) (cisplatin) is one of the most active antitumor agents used in human chemotherapy of non-small cell lung cancer. Cisplatin forms crosslinked DNA adducts and its cytotoxicity has been shown to be mediated by propagation of DNA damage recognition signals to downstream pathways prompting apoptosis. The steps involved in the process include changes in Ca(2+) signaling with dysregulated tumor cell turn-over. Stromal interaction molecules 1 (STIM1), as one of the most potent tumor suppressor genes, are identified as the endoplasmic-reticulum (ER) Ca(2+) sensor controlling store-operated Ca(2+) entry (SOCE) in non-excitable cells, which is main pathway to extracellular Ca(2+) influx. Its role in STIM1 cisplatin-induced apoptosis of non-small cell lung cancer was the focus of study with focus on SOCE inhibitors 2-APB- and SKF96365-cisplatin-induced apoptosis in the non-small cell lung cancer (NSCLC) cell lines A549 and H460. In this experimental model, cisplatin-induced apoptosis and decreased concentration of intracellular Ca(2+) was demonstrated. The expression of STIM1 was significantly higher in carcinoma tissue than in the adjacent non-neoplastic lung tissue. These findings support the conclusion that STIM1 may play an important role in the development of NSCLC which makes drugs that repress the expression of STIM1 to be a potential target for lung cancer therapy.
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Minhong
authors.initials: M
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Danmiao
authors.initials: D
authors.lastname: Lin
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering; D000071737:Stromal Interaction Molecule 1; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002945:Cisplatin
keywords: Apoptosis; Calcium; Cisplatin; Non-small cell lung cancer; SOC; STIM1