Cancer Research and Treatment

Original Articles

Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells: Miso Lee, Kyung-Hun Lee, Ahrum Min, Jeongeun Kim, Seongyeong Kim, Hyemin Jang, Jee Min Lim, So Hyeon Kim, Dong-Hyeon Ha, Won Jae Jeong, Koung Jin Suh, Yae-Won Yang, Tae Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2019;51(2):451-463. Published online June 6, 2018; DOI: https://doi.org/10.4143/crt.2017.341

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Purpose
Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells.
Materials and Methods
The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis.
Results
AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines.
Conclusion
Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

Citations

Citations to this article as recorded by

PIM1 attenuates cisplatin-induced AKI by inhibiting Drp1 activation
Yuzhen Li, Lang Shi, Fan Zhao, Yanwen Luo, Mingjiao Zhang, Xiongfei Wu, Jiefu Zhu
Cellular Signalling.2024; 113: 110969. CrossRef
Prognostic Model Construction of Disulfidptosis-Related Genes and Targeted Anticancer Drug Research in Pancreatic Cancer
Hongtao Duan, Li Gao, Aiminuer Asikaer, Lingzhi Liu, Kuilong Huang, Yan Shen
Molecular Biotechnology.2024;[Epub] CrossRef
PIM1 kinase and its diverse substrate in solid tumors
Rituparna Choudhury, Chandan Kumar Bahadi, Ipsa Pratibimbita Ray, Pragyanshree Dash, Isha Pattanaik, Suman Mishra, Soumya R. Mohapatra, Srinivas Patnaik, Kumar Nikhil
Cell Communication and Signaling.2024;[Epub] CrossRef
The evaluation of six genes combined value in glioma diagnosis and prognosis
Ping Lin, Lingyan He, Nan Tian, Xuchen Qi
Journal of Cancer Research and Clinical Oncology.2023; 149(13): 12413. CrossRef
Toxic effects of AZD1208 on mouse oocytes and its possible mechanisms
Feng‐Ze Yan, Ying‐Chun Ouyang, Tie‐Gang Meng, Hong‐Yong Zhang, Wei Yue, Xin‐Ran Zhang, Yue Xue, Zhen‐Bo Wang, Qing‐Yuan Sun
Journal of Cellular Physiology.2022; 237(9): 3661. CrossRef
Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects
Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(11): 129995. CrossRef
TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy
Jin Won Kim, Ahrum Min, Seock-Ah Im, Hyemin Jang, Yu Jin Kim, Hee-Jun Kim, Kyung-Hun Lee, Tae-Yong Kim, Keun Wook Lee, Do-Youn Oh, Jee-Hyun Kim, Yung-Jue Bang
Cancers.2020; 12(2): 334. CrossRef
PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension
Marie-Claude Lampron, Géraldine Vitry, Valérie Nadeau, Yann Grobs, Renée Paradis, Nolwenn Samson, Ève Tremblay, Olivier Boucherat, Jolyane Meloche, Sébastien Bonnet, Steeve Provencher, François Potus, Roxane Paulin
Arteriosclerosis, Thrombosis, and Vascular Biology.2020; 40(3): 783. CrossRef
Inhibition of PIM1 attenuates the stem cell–like traits of breast cancer cells by promoting RUNX3 nuclear retention
Hui Liu, Cheng Chen, Dongshen Ma, Yubing Li, Qianqian Yin, Qing Li, Chenxi Xiang
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Scientific Reports.2020;[Epub] CrossRef
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Soraya Alnabulsi, Enas A. Al-Hurani
Drug Discovery Today.2020; 25(11): 2062. CrossRef
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Maiara Bernardes Marques, Michael González-Durruthy, Bruna Félix da Silva Nornberg, Bruno Rodrigues Oliveira, Daniela Volcan Almeida, Ana Paula de Souza Votto, Luis Fernando Marins
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Korean Cancer Patients’ Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate: Yoojoo Lim, Jee Min Lim, Won Jae Jeong, Kyung-Hun Lee, Bhumsuk Keam, Tae-Yong Kim, Tae Min Kim, Sae-Won Han, Do Youn Oh, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(4):1033-1043. Published online April 7, 2017; DOI: https://doi.org/10.4143/crt.2016.413

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients.
Materials and Methods
From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea.
Results
A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026).
Conclusion
The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

Citations

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