Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
A Novel Small Molecule Inhibitor of MDM2-p53 (APG-115) Has Antitumor Activity in Gastric Adenocarcinoma
31 Pages Posted: 29 Mar 2019
More...Abstract
Gastric cancer (GC) is the third leading cause of cancer related death. APG-115, a novel MDM2-P53 inhibitor, is a potential anticancer agent. In this study, we aim to investigate the anticancer effect and mechanisms of APG-115 in GC. The anti-tumor activity of APG-115 was evaluated both in vitro and in vivo. Western blot analysis and siRNA interference for mechanism exploration of APG-115. We found that APG-115 exerted potent proliferation inhibition on p53 wild-type gastric cancer cells AGS and MKN-45 in a time-and dose-dependent manner. Besides, APG-115 could induce apoptosis and cell-cycle arrest in G1/G0 phase in the p53 wild-type gastric cancer cells. In vivo, APG-115 exhibited potent antitumor activity against human gastric cancer xenografts. Our data provide solid preclinical evidence that APG-115 can serve as an effective and precise therapeutic strategy for gastric cancer.
Funding Statement: This work was supported by Natural Science Foundation of Guangdong Province, China (grant no. 2018A030310260); Medical Scientific Research Foundation of Guangdong Province, China (grant no. 2018102516469945); National Natural Science Foundation of China (Grant number. 81602066 and 81772587); the Fundamental Research Funds for the Central Universities (Grant number. 16ykpy25); the third outstanding young talents training plan and Medical Scientist program of Sun Yat-sen University cancer center; Science and Technology Planning Project of Guangzhou, China (Grant number. 201510161726583); National Science and Technology Major Project, China (Grant number. 2016ZX09101004).
Declaration of Interests: The authors declare that they have no competing interests.
Ethics Approval Statement: All animal experiments were performed under the guidance of Sun Yat-Sen University Committee for Use and Care of Laboratory Animals and approved by the animal experimentation ethics committee.
Keywords: MDM2, p53, APG-115, Gastric cancer, Apoptosis
Suggested Citation: Suggested Citation