放射治疗过程中出现的自噬活性增强与放射敏感性之间的关系和机制备受争议。最新的研究发现p130cas对自噬和肿瘤治疗敏感性均有调节作用，但机制尚不十分清楚，在肺癌中照射对p130cas的影响及与自噬的关系尚无相关报道。我们发现照射可以上调p130cas的表达和磷酸化水平，增强自噬标记物LC3B的表达，降低肺癌细胞的放射敏感性。因此推测p130cas可能通过底物区域第6-15位酪氨酸磷酸化，调控JNK激活和DRAM基因转录，或使Bcl-2发生磷酸化，促使Beclin-1与Bcl-2解聚，从而增强自噬活性，降低放射敏感性。我们拟通过双向调控p130cas/JNK通路、构建p130cas不同结构域及不同磷酸化位点的突变体等方法，试图阐明肺癌中自噬与放射敏感性之间的关系及分子机制，为临床上放射治疗增敏和避免放射抵抗提供重要理论基础和实验依据。

The relationship and mechanism between enhanced autophagic activity appeared in the course of radiotherapy and radiosensitivity are controversial. A most recent study found that p130cas effected on both autophagy and tumor treatment sensitivity, but the underlying mechanisms remain unclear. Moreover, there were no relevant reports about the effect of irradiaion on p130cas expression and the relationship between ionizing radiation and autophagy. Our results showed that the irradiation can increase the expression of p130cas and phosphorylation levels, enhance the expression of autophagy marker LC3B and decrease the radiosensitivity of lung cancer cells. We hypothesized that p130cas may activate JNK through phosphorylated the No. 6-15 tyrosine phosphorylation sites at its substrate region, and then directly activated DRAM gene or facilitated the depolymerization between Beclin-1 and Bcl-2 by phosphorylated Bcl-2, which thus enhanced autophagic activity and reduce the radiation sensitivity. We intend to bidirectional regulation of p130cas/JNK pathway, constructing p130cas different domain and different phosphorylation site mutants. The aims of our study were to elucidate the relationship and mechanism between autophagy and radiosensitivity of lung cancer cells and to provide important theoretical and experimental basis for radiotherapy sensitization and radiation resistance prevention.