Overexpression of constitutive signal transducer and activator of transcription 3 mRNA in cisplatin-resistant human non-small cell lung cancer cells.
Non-small cell lung cancer (NSCLC) often shows intrinsic multidrug resistance, which is one of the most serious problems in cisplatin-based adjuvant chemotherapy. Recently, the constitutive activation of signal transducer and activator of transcription (STAT) factors has been found in a variety of human cancers. In the present study, the mRNA expression of STATs in various human NSCLC cell lines was investigated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) to determine whether STATs can be implicated in cisplatin resistance and apoptosis inducibility. Cisplatin triggered apoptosis in Ma-46 based on biochemical and morphological findings, but not in Ma-31. The mRNA expression of STAT3 was highest in cisplatin-resistant Ma-31 and lowest in cisplatin-sensitive Ma-46. A 6-hour exposure of cancer cells to cisplatin failed to stimulate STAT3 mRNA expression. Therefore, an increased transcriptional level of constitutive STAT3 may be related to the suppressive regulation of the apoptotic pathway in intrinsically chemo-resistant NSCLC cells.
Ikuta
Kenji
K
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan.
Takemura
Kazu
K
Kihara
Masaru
M
Nishimura
Masuhiro
M
Ueda
Nobuhiko
N
Naito
Shinsaku
S
Lee
Eibai
E
Shimizu
Eiji
E
Yamauchi
Aiko
A
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D002945:Cisplatin / Q000627:therapeutic use*; D053938:DNA Fragmentation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050796:STAT3 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D002945:Cisplatin