Background: Pancreatic cancer is generally acknowledged as the most common primary malignant tumor, and it is known to be resistant to conventional chemotherapy. Novel, selective antitumor agents are pressingly needed.
Methods: CCK-8 and colony formation assay were used to investigate the cell growth. Flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. The peroxide-sensitive fluorescent probe DCFH-DA was used to measure the intracellular ROS levels. Western blot assay was used to detect the levels of cell cycle and apoptosis related proteins. Xenografts in nude mice were used to evaluate the effect of Sophoridine on pancreatic cancer cell in vivo.
Results: Sophoridine killed cancer cells but had low cytotoxicity to normal cells. Pancreatic cancer cells were particularly sensitive. Sophoridine inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest at S phase and mitochondrial-related apoptosis. Moreover, Sophoridine induced a sustained activation of the phosphorylation of ERK and JNK. In addition, Sophoridine provoked the generation of reactive oxygen species (ROS) in pancreatic cancer cells. Finally, in vivo, Sophoridine suppressed tumor growth in mouse xenograft models.
Conclusion: These findings suggest Sophoridine is promising to be a novel, potent and selective antitumor drug candidate for pancreatic cancer.
[1]Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai 201203, Peoples R China.
[2]Shanghai Jiao Tong Univ, Dept Gen Surg, Xinhua Hosp, Sch Med, Shanghai 200092, Peoples R China.
[3]Shanxi Med Univ, Dept Gen Surg, Hosp 1, 85 South Jiefang Rd, Taiyuan 030001, Shanxi, Peoples R China.
(8.0+极速模式)