Lingling Zhu1, Shanshan Huang2, Junhe Li2, Jun Chen2, Yangyang Yao2, Li Li2, Hui Guo2, Xiaojun Xiang3, Jun Deng4, Jianping Xiong5. 1. Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China; Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, China. 2. Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China. 3. Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China. Electronic address: Xiangxiaojun30@163.com. 4. Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China. Electronic address: dengjun19871106@126.com. 5. Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China. Electronic address: Jpxiong0630@163.com.
Abstract
BACKGROUND: Sophoridine, a quinolizidine alkaloid extracted from the Chinese herb Sophora alopecuroides L., has been reported to exert antitumor effects against multiple human cancers. However, few studies have evaluated its tumor-suppressing effects and associated mechanism with respect to lung cancer, in addition to its potential to be used for clinical lung cancer treatment. METHODS: Different types of lung cancer cells were used to investigate the antitumor effects of sophoridine using cell viability, colony formation, and cell invasion, and migration assays. To determine the signaling pathways involved, western blot analysis, quantitative real-time polymerase chain reaction, an in vivo ubiquitination assay, and immunohistochemistry were used in cellular assays and with a subcutaneous xenograft model in BALB/c mice. RESULTS: Sophoridine significantly suppressed the proliferation of and colony formation by lung cancer cells in vitro. Transwell assays demonstrated that sophoridine also inhibited invasion and migration in lung cancer cells. In addition, sophoridine enhanced the effects of cisplatin on lung cancer cells. A mechanistic study revealed that sophoridine significantly activated the Hippo and p53 signaling pathways, and mouse xenograft experiments further confirmed in vitro findings in lung cancer cells. CONCLUSIONS: Taken together, these results suggest that sophoridine can inhibit lung cancer progression and enhance the effects of the anticancer drug cisplatin against lung cancer cells. The mechanism of action of sophoridine might involve the Hippo and p53 signaling pathways.
BACKGROUND:Sophoridine, a quinolizidine alkaloid extracted from the Chinese herb Sophora alopecuroides L., has been reported to exert antitumor effects against multiple humancancers. However, few studies have evaluated its tumor-suppressing effects and associated mechanism with respect to lung cancer, in addition to its potential to be used for clinical lung cancer treatment. METHODS: Different types of lung cancer cells were used to investigate the antitumor effects of sophoridine using cell viability, colony formation, and cell invasion, and migration assays. To determine the signaling pathways involved, western blot analysis, quantitative real-time polymerase chain reaction, an in vivo ubiquitination assay, and immunohistochemistry were used in cellular assays and with a subcutaneous xenograft model in BALB/c mice. RESULTS:Sophoridine significantly suppressed the proliferation of and colony formation by lung cancer cells in vitro. Transwell assays demonstrated that sophoridine also inhibited invasion and migration in lung cancer cells. In addition, sophoridine enhanced the effects of cisplatin on lung cancer cells. A mechanistic study revealed that sophoridine significantly activated the Hippo and p53 signaling pathways, and mouse xenograft experiments further confirmed in vitro findings in lung cancer cells. CONCLUSIONS: Taken together, these results suggest that sophoridine can inhibit lung cancer progression and enhance the effects of the anticancer drug cisplatin against lung cancer cells. The mechanism of action of sophoridine might involve the Hippo and p53 signaling pathways.