肺腺癌对放疗抵抗，薏苡仁提取物对其具有放射増敏作用，但机制不清，且临床无标志物预测疗效使治疗缺乏针对性。我们的研究显示放疗同时给予薏苡仁提取物能减少部分肺腺癌患者循环肿瘤DNA数量，体外试验发现薏苡仁提取物能增加肺腺癌细胞INPP4B蛋白表达抑制p-AKT表达。本课题检测不同基因型肺腺癌细胞INPP4B表达情况，同时观察薏苡仁提取物、放疗及联合作用后细胞内INPP4B变化，采用经典的克隆形成试验和裸鼠移植瘤模型检测薏苡仁提取物放射増敏作用，分析INPP4B与増敏作用之间的关系，通过多种分子生物学手段进行验证，以期揭示INPP4B是预测薏苡仁提取物放射增敏作用的标志物；在此基础上本研究还探讨薏苡仁提取物和放疗联合作用后能刺激INPP4B表达通过调控p-AKT影响细胞周期、细胞凋亡、DNA损伤和修复的放射増敏作用机制。课题为更好研究薏苡仁提取物放射增敏作用和寻找临床治疗获益人群提供实验室依据。

Lung adenocarcinoma is resistant to radiotherapy, coix seed extract can radiosensitize it. However, the mechanisms of radiosensitization are not clear and the therapy is not targeted because there is no biomarker to predict its clinical effect. Our previous study showed that circulating tumor DNA reduced in part of lung adenocarcinoma patients received radiotherapy and coix seed extract. Moreover, coix seed extract could increase INPP4B expression and inhibit p-AKT activation in vitro. Our present study detects INPP4B expression in a panel of lung adenocarcinoma cell lines with different genotypes. We also observe the alterations of INPP4B expression induced by coix seed extract, radiotherapy and combined therapy. Next, we use classical clonogenic assay and xenograft tumor growth assay to test the radiosensitizaiton of coix seed extract, analyse the relationship between the effect of radiosensitization and INPP4B. Various molecular biological methods are employed to verify the differences. Through the above observations, we hope to confirm that INPP4B is the biomarker to predict the radiosensitizaion effect of coix seed extract. Besides, the present study explores the mechanisms of radiosensitizaion of coix seed extract are through increasing INPP4B expression, inhibiting p-AKT activation then influencing cell cycle, apoptosis, DNA damage and repair. The project may provide theoretical basis for the use of coix seed extract combined radiotherapy treating lung cancer and finding patients who can benefit from the treatment.