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.
Keywords: HIF-1α; NSCLC; PI3K/Akt; insufficient RFA; proliferation.
© The Author 2016. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.