ABSTRACT
Background and purpose:Hypoxia induced the decreased radiosensitivity of tumor cells, which was the cause of tumor radioresistance and relapse and metastasis. During the course, HIF-1a played the most important role in the regulation of hypoxia. However, it’s still unknown about the effect of HIF-1a on the radiosensitivity of hypoxia tumor cells and the relationship with autophagy. This study was to inhibit HIF-1αexpression in hypoxic lung adenocarcinoma cell line A549 with RNA interference (RNAi), and explore its effect on hypoxic cell radiosensitivity and autophagy. Methods: Plasmids pHIF-1α-shRNA and Neg-shRNA (negative control) were constructed and transfected into hypoxic A549 cells, this positive clone was named A549/HIF-1α-shRNA. Clone formation array was applied to calculate the value of D0, SF2, SER. The expression of HIF-1α, LC3, c-parp was detected by Western blot. Results:The SF2 of hypoxic A549 cell was 0.62, which was higher than that of normoxic A549 cell, SER was 1.45. The level of LC3Ⅱincreased significantly and the level of c-parp decreased after the radiation of hypoxic A549 cell. The level of HIF-1a increased in hypoxic A549 cells. The expression of HIF-1αin hypoxic A549 cells was suppressed markedly after transfection of HIF-1α-shRNA;this clone was named A549/HIF-1α-shRNA. The SF2 and SER were significantly lower in A549/HIF-1α-shRNA cells, 0.45 and 0.72 respectively. Under the hypoxic condition and after the inhibition of HIF-1α, the expression of LC3Ⅱ decreased significantly and the expression of c-parp increased. Conclusion:We successfully established a cell model that HIF-1αexpression was suppressed almost completely by RNAi. The inhibition of HIF-1αby shRNA may raise the radiosensitivity and decrease the autophagy of hypoxic A549 cells in vitro.
ABSTRACT
Background and purpose:To improve the quality of life of patients with advanced non-small cell lung cancer is one of the problems which the oncologists have to be aware of. Gefi tinib has been used to treat advanced non-small cell lung cancer. We studied the effect of gefi tinib in the improvement of quality of life of patients with advanced non-small cell lung cancer. Methods:There were 70 patients with advanced non-small cell lung cancer treated in our cancer center. One oral gefi tinib tablet(250 mg) was administered every day without interruption unless disease progression or unacceptable toxicity occurred. The impact of treatment on disease-related symptoms and quality of life(QoL) were evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer Quality of Life Questionnaires(EORTC QLQ-C30 and QLQ-LC13) . Results:58 patients finished the questionnaires. The mean scores of fi ve functional scales(physical,role,emotional cognitional and social) were 63,56,68,65,61 respectively after eight weeks of treatment,compared to 52,49,64,60,52 respectively before treatment,and the mean score of global QoL after and before treatment were 60 and 53 respectively. There were statistical differences in fi ve functional scales and global QoL(P