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Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncology. The hypoxia-inducible factor (HIF)-1α plays a crucial role in radiosensitivity, but the detailed mechanisms remain elusive. A relationship has been suggested to exist between hypoxia and autophagy recently. In the current study, we studied the effect of hypoxia-induced autophagy on radioresistance in lung cancer cell lines. A549 and H1299 cells were cultured under normoxia or hypoxia, followed by irradiation at dosage ranging from 0 to 8 Gy. Clonogenic assay was performed to calculate surviving fraction. EGFP-LC3 plasmid was stably transfected into cells to monitor autophagic processes. Western blotting was used to evaluate the protein expression levels of HIF-1α, c-Jun, phosphorylated c-Jun, Beclin 1, LC3 and p62. The mRNA levels of Beclin 1 were detected by qRT-PCR. We found that under hypoxia, both A549 and H1299 cells were radio-resistant compared with normoxia. Hypoxia-induced elevated HIF-1α protein expression preferentially triggered autophagy, accompanied by LC3 induction, EGFP-LC3 puncta and p62 degradation. In the meantime, HIF-1α increased downstream c-Jun phosphorylation, which in turn upregulated Beclin 1 mRNA and protein expression. The upregulation of Beclin 1 expression, instead of HIF-1α, could be blocked by SP600125 (a specific inhibitor of c-Jun NH2-terminal kinase), followed by suppression of autophagy. Under hypoxia, combined treatment of irradiation and chloroquine (a potent autophagy inhibitor) significantly decreased the survival potential of lung cancer cells in vitro and in vivo. In conclusion, hypoxia-induced autophagy through evaluating Beclin1 expression may be considered as a target to reverse the radioresistance in cancer cells.

9.Urgent tracheal resection and reconstruction assisted by temporary cardiopulmonary bypass: a case report.

Hui GAO ; Bin ZHU ; Jie YI ; Tie-hu YE ; Yu-guang HUANG

Chinese Medical Sciences Journal 2013;28(1):55-57

Severe tracheal stenosis can not only cause critical medical problems such as severe shortness of breath, hypoxia, and even orthopnea, but also impose overwhelming challenges on the physicians, particularly the anesthesiologist. Life-threatening airway obstruction can make the patient's gas exchange extremely difficult.Though several options could be offered regarding the treatment of tracheal stenosis, normally, tracheal resection and following reconstruction is the first choice for severe airway stenosis. Successful surgical intervention relies on the close communication and cooperation between surgeons and anesthesiologists. In these cases, airway management is the top issue for the anesthesiologist, and the level of difficulty varies with stenosis location, severity of stenosis, and surgical technique. Extracorporeal membrane oxygenation (ECMO), or cardiopulmonary bypass (CPB), is rarely utilized for the surgery, but for those impossible airways due to nearly complete tracheal obstruction, ECMO or CPB could be the final choice for anesthesiologists. Here we report a case of successful urgent airway management for tracheal resection and reconstruction assisted by temporary CPB.
Cardiopulmonary Bypass ; Emergencies ; Female ; Humans ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Trachea ; surgery