title: Insufficient radiofrequency ablation promotes the growth of non-small cell lung cancer cells through PI3K/Akt/HIF-1α signals.
abstract: Accelerated progression of residual non-small cell lung cancer (NSCLC) after incomplete radiofrequency ablation (RFA) has frequently been reported. In this study, NSCLC cells A549, CCL-185, and H358 were treated using a water bath at 47°C for 5, 10, 15, 20, and 25 min gradually to establish the sublines A549-H, CCL-185-H, and H358-H, respectively. A549-H, CCL-185-H, and H358-H cells showed a significant increase in proliferation rate when compared with their corresponding parental cellsin vitro The expression of hypoxia-inducible factor-1α (HIF-1α) was obviously upregulated in both A549-H and CCL-185-H cells. Silencing of HIF-1α abolished the insufficient RFA-induced proliferation in A549-H and CCL-185-H cells. Furthermore, insufficient RFA treatment markedly elevated the phosphorylation of ERK1/2 and Akt, but not of p38 MAPK or JNK, in A549-H and CCL-185-H cells. The inhibitor of Akt, LY294002, but not the inhibitor of ERK1/2, PD98059, suppressed the upregulation of HIF-1α and the proliferation of A549-H and CCL-185-H cellsin vitro Thein vivoresults confirmed that insufficient RFA could trigger the tumor growth, upregulate the HIF-1α expression, and activate Akt in A549 xenograft tumors. Our data suggest that insufficient RFA can promote thein vitroandin vivogrowth of NSCLC via upregulating HIF-1α through the PI3K/Akt signals.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Kang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China zhangrqamu@163.com.
authors.forename: Renquan
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D064593:Heterografts; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: HIF-1α; NSCLC; PI3K/Akt; insufficient RFA; proliferation