NDLI: Dual inhibitor of PI3K and mTOR (NVP-BEZ235) augments the efficacy of fluorouracil on gastric cancer chemotherapy

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

Dual inhibitor of PI3K and mTOR (NVP-BEZ235) augments the efficacy of fluorouracil on gastric cancer chemotherapy

Content Provider	Scilit
Author	Li, Liangqing Zhang, Shengwei Xie, Diya Chen, Hui Zheng, Xuelan Pan, Dun
Copyright Year	2018
Description	Dual inhibitor of PI3K and mTOR (NVP-BEZ235) augments the efficacy of fluorouracil on gastric cancer chemotherapy Liangqing Li, Shengwei Zhang, Diya Xie, Hui Chen, Xuelan Zheng, Dun Pan Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China Purpose: NVP-BEZ235 is a recently developed dual inhibitor of PI3K and mTOR and shows good inhibitory effects on several types of tumors. However, the efficacy of NVP-BEZ235 on gastric cancer therapy remains unclear. This study aimed to investigate the potential of NVP-BEZ235 as a new agent to enhance chemotherapy for gastric cancer. Methods: Human gastric cancer MKN-45 cells or nude mice xenografted with MKN-45 cells were treated by NVP-BEZ235 and fluorouracil (5-FU) alone or in combination. The proliferation, invasion, apoptosis, and chemoresistance of gastric cancer cells were examined in vivo and in vitro. Results: In vitro, combined treatment with NVP-BEZ235 and 5-FU showed synergistic inhibitory effects on proliferation, migration, and invasion and synergistic stimulating effects on apoptosis of MKN-45 cells. In vivo, NVP-BEZ235 and 5-FU synergistically inhibited the growth and induced apoptosis of MKN-45 xenografts. Mechanistically, NVP-BEZ235 inhibited PI3K/Akt/mTOR signaling; decreased the levels of Bcl-2, MMP9, and VEGF; but increased the levels of Bax and cleaved caspase-3 in MKN-45 xenografts. Conclusion: NVP-BEZ235 enhances the antitumor efficacy of 5-FU. Therefore, NVP-BEZ235 is a promising agent to enhance chemotherapy for gastric cancer. Keywords: NVP-BEZ235, fluorouracil, gastric cancer, chemotherapy, P13K, mTOR
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158000/pdf https://www.dovepress.com/getfile.php?fileID=44605
Ending Page	6118
Page Count	8
Starting Page	6111
ISSN	11786930
DOI	10.2147/ott.s172957
Journal	OncoTargets and therapy
Volume Number	11
Language	English
Publisher	Informa UK Limited
Publisher Date	2018-09-01
Access Restriction	Open
Subject Keyword	Journal: Oncotargets and Therapy Oncology Nvp-bez235 P13k Chemotherapy Fluorouracil Gastric Cancer Mtor
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical) Oncology

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