Oxaliplatin Induces Apoptosis Through ROS Mediated PUMA Expression In Colon Cancer

Colorectal cancer is a major health problem in China, representing the third highest cause of cancer mortality in alimentary tract and has a trend to increase. It is important to develop early diagnosis and more effective therapy. Although surgery is the first therapeutic choice, combining chemotherapy is necessary due to the high recurrence rate and late diagnosis. Oxaliplatin, a platinum compound, is one of the most effective drugs for its better effect on resistant cases and fewer side effects comparing with cisplatin and carboplatin. Inducing cancer cells to apoptosis is the important mechanism of oxaliplatin, but the precise molecular mechanism involved in a series of genes. In previous study, PUMA, a novel and important member of Bcl-2 family, plays an important role in stress-induced apoptosis and is regulated by p53 directly. Here we report that oxaliplatin induced PUMA expression in a dose-and time-dependent manner. Oxaliplatin-induced PUMA expression was p53-independent. Oxaliplatin induced apoptosis was abrogated by suppression of PUMA expression. Oxaliplatin-induced PUMA expression and apoptosis was decreased by antioxidant. Taken together, our data show that PUMA plays an important role in oxaliplatin- and H2O2- induced apoptosis and oxaliplatin induced PUMA expression by increasing the concentration of ROS in colon cancer. Thisstudy will be of great help in both elucidating the molecular mechanism of anticancer drug and finding the vital genes in chemotherapy. Given the important role of PUMA in apoptosis of colon cancer cells, our present study also suggests that PUMA may be a good target for cancer gene therapy.