Screening of potential cancer cell lines on white adipose browning and lipolysis

• Main Authors: Chi-Chang Huang, 黃啟彰
• Other Authors: Shih-Torng Ding
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/d296qu

碩士 === 國立臺灣大學 === 動物科學技術學研究所 === 106 === Beige adipocytes are a subset of white adipocytes which can dissipate heat under certain stimuli through mitochondrial uncoupling protein 1 (UCP1). Similar to brown adipocytes, high mitochondrial content and energy-consuming characteristic of brown/beige adipocytes have been regarded as a therapeutic target against obesity-related metabolic diseases. Cancer-associated cachexia (CAC) is a wasting syndrome frequently found in advanced cancer patients with emaciation, muscle weakness and metabolic disorders. Switch of energy-depositing ‘‘bad fat’’ into energy-wasting ‘‘good fat’’ might address a lethal accomplice to cachectic patients. UCP1 expression can be detected in adipose tissues of several cancer models including lung, breast, and pancreatic cancers, suggesting that tumor cells exacerbate cancer progression by operating at adipose thermogenesis. To verify whether the cancer cells can stimulate adipose thermogenesis-related gene expression, conditioned media from pancreatic (Panc-1, BxPC-3, HPAC, MIA-PaCa-2, Capan-1, and Capan-2) and breast (MDA-MB-231 and 4T-1) cancer cell lines were harvested and used to treat mouse cell line 3T3-L1 and primary subcutaneous adipocytes (C57BL/6). The real-time qPCR was conducted to evaluate the thermogenic (Ucp1, Cidea, Dio2, Prdm16, Cox7a, and Cox8b) and lipolysis-related (Atgl and Hsl) gene expression. UCP1 protein level was also determined by Western blotting. Oil-Red O and glycerol release assay were performed for lipid droplet contents and lipolysis. Our results showed that conditioned medium of pancreatic cell line Capan-1 for 3T3-L1, and conditioned medium from breast MDA-MB-231 and 4T-1 for primary adipocyte culture, moderately up-regulated thermogenic gene expression. UCP1 protein expression was higher in adipocytes treated with conditioned-medium of HPAC, Capan-1, or MDA-MB-231 compared to the control group. Analysis of Oil-Red O and glycerol release showed no difference by the different cancer cell derived conditioned media. Taken together, cancer cells might possess differential effects on thermogenic gene expression in adipocytes. Among cell lines used in the study, pancreatic HPAC and Capan-1, breast cancer MDA-MB-231 and 4T-1 partially up-regulated thermogenic gene expression in adipocytes, suggesting the existence of factors in cancer conditioned medium involved in thermogenesis initiation in adipocytes. The identification of the factors that mediates the browning effect can be application in developing strategies for coping with cancer cachexia.