机构：[1]Department of Interventional Radiology, Wujiang Hospital Affiliated to Nantong University, Wujiang, Suzhou, China[2]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China[3]Department of Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, 215300, China
The current research studied the potential effect of autophagy on icaritin-induced anti-colorectal cancer (CRC) cell activity. Treatment of icaritin in both primary and established (HT-29) CRC cells induced feedback activation of autophagy, evidenced by p62 degradation, Beclin-1 and autophagy-related gene-5 (ATG-5) upregulation, as well as light chain 3B (LC3B)-GFP puncta formation. Pharmacological inhibiting of autophagy dramatically potentiated icaritin-induced CRC cell death and apoptosis. Meanwhile, shRNA-mediated knockdown of Beclin-1 or ATG-5 also sensitized icaritin-induced CRC cell death and apoptosis. Icaritin activated AMP-activated protein kinase (AMPK) signaling in CRC cells, functioning as the upstream signaling for autophagy activation. shRNA/siRNA-mediated knockdown of AMPKa1inhibited icaritin-induced autophagy activation, but exacerbated CRC cell death. On the other hand, the AMPK activator compound 13 (C13) or the autophagy activator MHY1485 attenuated icaritin-induced cytotoxicity. In nude mice, icaritin (oral administration)-induced HT-29 tumor growth inhibition was potentiated when combined with AMPKa1 shRNA knockdown in tumors. We conclude that feedback activation of AMPK-autophagy pathway could be a primary resistance factor of icaritin.
基金：
The study was supported by WuJiang Science Bureau and the National Natural Science Foundation of China (81472786), the Foundation of tumor clinical and basic research team of Kunshan First People’s Hospital (KYC005).
第一作者机构：[1]Department of Interventional Radiology, Wujiang Hospital Affiliated to Nantong University, Wujiang, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Interventional Radiology, Wujiang Hospital Affiliated to Nantong University, Wujiang, Suzhou, China[3]Department of Oncology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, 215300, China
医学