PAC exhibits potent anti‐colon cancer properties through targeting cyclin D1 and suppressing epithelial‐to‐mesenchymal transition

摘要: Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide. Although response rates overall survival have been improved in recent years, resistance to multiple drug combinations inevitable. Therefore, the development more efficient drugs, with fewer side effects urgently needed. To this end, we investigated present report effect PAC, novel cucumin analogue, on CRC cells both vitro vivo. We shown that PAC induces apoptosis, mainly via internal mitochondrial route, inhibits cell proliferation through delaying cycle at G2/M phase. Interestingly, pro-apoptotic was mediated STAT3-dependent down-regulation cyclin D1 its downstream target survivin. Indeed, change expression level modulated survivin PAC. Furthermore, using ChIP assay, PAC-dependent reduction binding STAT3 promoter Additionally, suppressed epithelial-to-mesenchymal process down-regulating mesenchymal markers (N-cadherin, vimentin Twist1) inhibiting invasion/migration abilities repressing pro-migration/invasion protein kinases AKT ERK1/2. In addition, inhibited tumor growth repressed JAK2/STAT3, AKT/mTOR MEK/ERK pathways as well their common effectors humanized xenografts. Collectively, these results indicate has potent anti-CRC effects, therefore could constitute an effective alternative chemotherapeutic agent, which may consolidate adjuvant treatment colon cancer. © 2015 Wiley Periodicals, Inc.