Silencing of TRPM8 inhibits aggressive tumor phenotypes and enhances gemcitabine sensitivity in pancreatic cancer
| Autor: | Bin He, Yujing Gong, Jiefeng Liu, WangHao Li, ZhiGuo He, Yiping Liu, WenJie Hao, Qianle Yu, ZiChao He, Guohuang Hu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Antimetabolites Antineoplastic Endocrinology Diabetes and Metabolism medicine.medical_treatment TRPM Cation Channels Deoxycytidine 03 medical and health sciences 0302 clinical medicine Pancreatic cancer Cell Line Tumor Medicine Gene silencing Humans Neoplasm Invasiveness Gene Silencing RNA Small Interfering Aged Cell Proliferation Gene knockdown Chemotherapy Hepatology business.industry Cell growth Gastroenterology Middle Aged medicine.disease Prognosis Combined Modality Therapy Gemcitabine Multidrug Resistance-Associated Protein 2 Pancreatic Neoplasms 030104 developmental biology Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Disease Progression Adenocarcinoma Calcium Female business medicine.drug |
| Zdroj: | Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 18(8) |
| ISSN: | 1424-3911 |
| Popis: | The transient receptor potential TRPM8 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates the function of TRPM8, we examined its role in the proliferation and invasion of pancreatic cancer (PC) cells. TRPM8 expression increased in both the PC tissues and cell lines; a high TRPM8 expression was correlated with poorer prognosis in patients with PC. In PC cell lines, PACN-1 and BxPC-3, Ca2+ influxes could be evoked by TRPM8; the sensitivity of PC cells to gemcitabine was increased, while the proliferation and invasion of PC cells were suppressed after RNA interference-mediated silencing of TRPM8. The mechanism of TRPM8 in gemcitabine-based chemotherapy was then investigated. The expression and activity of multidrug resistance-associated proteins, P-gp, MRP-2, LRP, was significantly reduced in response to TRPM8 silence. Moreover, TRPM8 knockdown significantly increased hENT1 protein levels and the ratio of Bax/Bcl-2 while decreased the protein levels of RRM1. Thus, TRPM8 is required for PC cell proliferation and invasion and was closely related to the gemcitabine sensitivity of PC. The modulation of TRPM8 expression may help improve treatment response of PC by combining with traditional chemotherapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect