Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway.
Previous reports have implicated epithelial-mesenchymal transition (EMT) as a major cause of cancer. TWIST, a novel zinc finger transcription factor, was suggested to be an important inducer of EMT and therefore be involved in different phases of tumorigenicity. However, whether TWIST suppression could increase chemosensitivity of cancer cells to chemotherapeutic agent remains unclear. In the present study, we utilized RNA interference to knockdown TWIST expression in A549 cells and further assessed the cell viability and apoptosis as well as possible MAPKs and mitochondrial pathways. The data showed that TWIST depletion significantly sensitized A549 cells to cisplatin by inducing activation of JNK/mitochondrial pathway but not ERK and p-38 pathways, suggesting critical roles of TWIST in A549 cell chemoresistance to cisplatin and raising the possibility of TWIST depletion as a promising approach to lung cancer therapy.
Zhuo
Wen-Lei
WL
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Wang
Yan
Y
Zhuo
Xian-Lu
XL
Zhang
Yun-Song
YS
Chen
Zheng-Tang
ZT
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000201:enzymology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D016335:Zinc Fingers
D000970:Antineoplastic Agents; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin