NDLI: NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction

Please wait, while we are loading the content...

NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction

Content Provider	Semantic Scholar
Author	Yang, Shida Li, Xin Guan, Wenchang Qian, Mingqin Yao, Zhicheng Yin, Xiaoxue Zhao, Hongmei
Copyright Year	2017
Abstract	NVP-BKM120, a potent and highly selective PI3K inhibitor, is currently being investigated in phase I/II clinical trials. The mechanisms of action of NVP-BKM120 in colon cancer cells are unclear. In the present study, we investigated how NVP-BKM120 suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. We found that NVP-BKM120 treatment enhance PUMA induction irrespective of p53 status through the FoxO3a pathway following AKT inhibition. Furthermore, PUMA is required for NVP-BKM120-induced apoptosis in colon cancer cells. In addition, NVP-BKM120 also synergized with 5-Fluorouracil or regorafenib to induce marked apoptosis via PUMA induction. Deficiency of PUMA suppressed apoptosis and antitumor effect of NVP-BKM120 in xenograft model. These results demonstrate a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications.
Starting Page	83052
Ending Page	83062
Page Count	11
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=20943&path%5B%5D=66694
PubMed reference number	29137323v1
Alternate Webpage(s)	https://doi.org/10.18632/oncotarget.20943
DOI	10.18632/oncotarget.20943
Journal	Oncotarget
Volume Number	8
Language	English
Access Restriction	Open
Subject Keyword	1-Phosphatidylinositol 3-Kinase Apoptosis BKM120 Bcl-2-Binding Component 3 Colon Carcinoma FOXO3A protein, human Fluorouracil NVP ABE171 NVP ADW742 Nevirapine Proto-Oncogene Proteins c-akt cancer cell cell growth pan-PIM Kinase Inhibitor NVP-LGB-321 regorafenib
Content Type	Text
Resource Type	Article

Central Library (ISO-9001:2015 Certified)
Indian Institute of Technology Kharagpur
Kharagpur, West Bengal, India | PIN - 721302

See location in the Map
03222 282435
Mail: support@ndl.gov.in

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in