Short hairpin RNA targeting AKT1 and PI3K/p85 suppresses the proliferation and self-renewal of lung cancer stem cells.
The aim of the present study was to investigate the effect of short hairpin (sh)RNA targeting AKT1 and phosphatidylinositol 3-kinase (PI3K)/p85 on the proliferation and self-renewal of lung cancer stem cells (LCSCs). The recombinant adenovirus expression vector, which contained shRNA targeting open reading frames of AKT1 and PI3K/p85, was transfected into LCSCs. It was found that AKT1 and PI3K/p85 expression was upregulated in LCSCs compared with that in the primary lung cancer cells. Recombinant adenovirus vector rAd5-siAKT1-siPI3K/p85 significantly downregulated AKT1 and PI3K/p85 mRNA and protein expression in LCSCs. The downstream factors, proliferating cell nuclear antigen (PCNA) and cyclin D1 were also downregulated, while p53 was upregulated. Following silencing of AKT1 and PI3K/p85, cell proliferation, tumor sphere formation and tumor formation in NOD/SCID mice were also reduced. According to the present results, it was hypothesized that the PI3K/Akt signaling pathway is important in the self‑renewal and proliferation of LCSCs, and that targeting the PI3K/Akt signaling pathway decreases the rate of tumor formation in vivo.
Department of Respiratory Medicine, Taizhou People's Hospital Affiliated to Medical College of Nantong University, Taizhou, Jiangsu 225300, P.R. China.
Ai-Gui
AG
Jiang
Department of Respiratory Medicine, Taizhou People's Hospital Affiliated to Medical College of Nantong University, Taizhou, Jiangsu 225300, P.R. China.
Hui-Yu
HY
Lu
Department of Oncology, Taizhou People's Hospital Affiliated to Medical College of Nantong University, Taizhou, Jiangsu 225300, P.R. China.
De-Geng
DG
Zhang
Institute of Clinical Medicine, Taizhou People's Hospital Affiliated to Medical College of Nantong University, Taizhou, Jiangsu 225300, P.R. China.
Li-Xin
LX
Zhang
Department of Respiratory Medicine, Taizhou People's Hospital Affiliated to Medical College of Nantong University, Taizhou, Jiangsu 225300, P.R. China.
Xiao-Yan
XY
Gao
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000081082:Phosphoinositide-3 Kinase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt