The Treatment and Mechanism of Dihydroisotanshinone I in Primary and Bone Metastasis of Lung Cancer

According to the 2012 cancer registry annual report of Taiwan, lung cancer is the 4th common malignant disease and the 1st leading cause of death in cancer patients. About half of new cases were diagnosed at advanced stages of lung cancer. For advanced lung cancer, bone is the major metastasis site. The treatments include surgery, chemotherapy, or radiotherapy for advanced lung cancer. However, the effectiveness of the treatments is limited. Therefore, developing regimens for treating advanced lung cancer that are more effective and have minimal adverse effects is extremely important in lung cancer research. Tanshinones, the major constituents of danshen, show antibacterial, antioxidant, and antineoplastic activities. For lung cancer, our current study finds that dihydroisotanshinone I (application for US patent), a bioactive compound from tanshinones, inhibits the migration ability of both a human lung adenocarcinoma cell line (A549 cells) and human lung large cell carcinoma cell line (H460 cells). Dihydroisotanshinone I also interrupts the crosstalk between macrophages and lung cancer cells through regulating the CCL2 signal pathway. This study will expand what we already know to investigate the anti-lung tumor effects of dihydroisotanshinone I and its underlying mechanism. We will also investigate how dihydroisotanshinone I prevents bone metastasis of lung cancer. Moreover, we hope to assess the effects of dihydroisotanshinone I treatment on lung cancer in an animal model. The proposal will be performed through these following aims: Aim-1 ： Primary screening of anti-tumor effect and mechanism from dihydroisotanshinone I Aim-2 ： To explore the anti-bone metastasis effect and underlying mechanism of dihydroisotanshinone I in lung cancer cell Aim-3 ： To investigate the anti-tumor and anti-metastasis effect of dihydroisotanshinone I in xenograft nude mice Overall, the success of this study will offer evidence that dihydroisotanshinone I is a promising therapeutic agent in treating lung cancers and preventing bone-metastasis. This study will benefit the development of methods for treating lung cancers.

Project ID:PC10701-0076
External Project ID:MOST105-2320-B182-006-MY3