Abstract
Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Particularly, a large number of patients with CRC also have liver metastasis. Currently, there are just a few targeted drugs against these two kinds of tumors which can only benefit a very small population of patients. Therefore, the need of more effective therapeutic drugs or strategies for these two types of cancers is urgent. PS341 (Bortezomib) is the first proteasome inhibitor drug which has been approved in clinical treatment for multiple myeloma. Here we demonstrated that PS341 negatively regulated HCC and CRC both in vitro and in vivo, including the inhibition of cell proliferation, epithelial-mesenchymal transition (EMT), the expression of stemness-related genes, cell migration and invasiveness. Mechanically, PS341 upregulated the expression of FOXO3, which inhibited the transcriptional activation of CTNNB1. The downregualtion of CTNNB1 led to apoptosis, cell cycle arrest, and the inhibition of migration, invasion, self-renewal and tumor formation of these two cancer types. In sum, our findings shed light on the PS341 mediated targeted therapy against both HCC and CRC in the future.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the most common liver cancer[1]
Our results showed clearly that PS341 could significantly suppress the proliferation, migration, epithelial-mesenchymal transition (EMT) and the expression of stemness-related gene of HCC and colorectal cancer (CRC) cells both in vitro and in vivo with the upregulation of FOXO3 and downregulation of CTNNB1, which shed some light on the future HCC and CRC treatment based on PS341
In order to identify the potential role of PS341 in HCC and CRC therapy, we first examined the function of PS341 in two HCC cell lines HepG2 and Huh[7] and two CRC cell lines HT29 and LoVo, respectively
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the most common liver cancer[1]. It is highly meaningful to develop novel and potent molecular targeted drugs for HCC In western countries such as Europe and USA, primary HCC is less common than liver metastases which mostly develop from colorectal cancers (CRCs)[6].Colorectal cancer is one of the largest reasons for morbidity and mortality caused by cancers[6,7]. There are currently three drugs together with four available drugs for targeted therapy against metastatic colorectal cancer[8] All these drugs can only benefit a small group of patients depending on their genetic signatures and many new targeted drugs are in urgent need to be developed in the future[8]. Our results showed clearly that PS341 could significantly suppress the proliferation, migration, EMT and the expression of stemness-related gene of HCC and CRC cells both in vitro and in vivo with the upregulation of FOXO3 and downregulation of CTNNB1, which shed some light on the future HCC and CRC treatment based on PS341
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
