Low-dose orlistat promotes the therapeutic effect of oxaliplatin in colorectal cancer
The failure of and resistance to oxaliplatin (OXA)-based chemotherapies may lead to poor prognosis in colorectal cancer (CRC) patients. It has been reported that orlistat (Orli) exhibits potent antitumor effects in several malignant tumors. Here, we identified that OXA in combination with low-dose Orli could sensitize CRC cells to OXA and induce marked synergistic apoptosis in vitro and in vivo. The potential synergistic effects were confirmed and quantified by in silico analysis. Furthermore, we validated the synergistic anti-tumor effects in CRC PDX mice model. A qPCR array was performed to evaluate the changes in 85 apoptosis-related genes to elucidate the possible molecular mechanisms in combination-induced cytotoxicity. To conclude, the antitumor synergistic effects of OXA and Orli make them effective and promising candidates for cancer treatment.
Orlistat and Hydroxycitrate Ameliorate Colon Cancer in Rats: The Impact of Inflammatory Mediators
Colon cancer (CC) is the third type of cancer worldwide. This study aimed to investigate the possible protective effects of orlistat and hydroxycitrate (HCA) against dimethylhydrazine (DMH) and high-fat diet (HFD)-induced CC in adult male rats. The rats were divided into ten groups including the normal group. The rats were treated with the DMH/HFD, orlistat (32 mg/kg), orlistat/DMH, orlistat/DMH/HFD, HCA (135 mg/kg), HCA/DMH, HCA/DMH/HFD, DMH (40 mg/kg), and HFD (20%) for 16 weeks. Administration of orlistat and HCA improved the measured markers of a colon tumor, inflammatory mediators, oxidative stress, as well as caspase-3 (an apoptotic marker) in the colon tissue compared with the CC group. Furthermore, orlistat and HCA corrected the histopathological lesions in the colon lining. These findings revealed that orlistat and HCA had a positive chemopreventive efficacy and could be viewed as a possible clinical solution for colon cancer.