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Lee JH, Chung KS, Lee HH, et al. Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells. Biomed Pharmacother. 2021;142:111961doi: 10.1016/j.biopha.2021.111961.
Lee, J. H., Chung, K. S., Lee, H. H., Ko, D., Kang, M., Yoo, H., Ahn, J., Lee, J. Y., & Lee, K. T. (2021). Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 142111961. https://doi.org/10.1016/j.biopha.2021.111961
Lee, Jeong-Hun, et al. "Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells." Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie vol. 142 (2021): 111961. doi: https://doi.org/10.1016/j.biopha.2021.111961
Lee JH, Chung KS, Lee HH, Ko D, Kang M, Yoo H, Ahn J, Lee JY, Lee KT. Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells. Biomed Pharmacother. 2021 Oct;142:111961. doi: 10.1016/j.biopha.2021.111961. Epub 2021 Jul 28. PMID: 34329824.
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Biomed Pharmacother. 2021 Oct;142:111961. doi: 10.1016/j.biopha.2021.111961. Epub 2021 Jul 28.

Improved tumor-suppressive effect of OZ-001 combined with cisplatin mediated by mTOR/p70S6K and STAT3 inactivation in A549 human lung cancer cells.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Jeong-Hun Lee, Kyung-Sook Chung, Hwi-Ho Lee, Dohyeong Ko, Minji Kang, Ho Yoo, JooHoon Ahn, Jae Yeol Lee, Kyung-Tae Lee

Affiliations

  1. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea; Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea.
  2. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea.
  3. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
  4. ONCOZEN Co., Ltd., ONCOZEN R&D Center, C-713, Beobwon-ro 11-gil, Songpa-gu, Seoul 05836, Republic of Korea.
  5. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: [email protected].
  6. Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea; Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Seoul 02447, Republic of Korea. Electronic address: [email protected].

PMID: 34329824 DOI: 10.1016/j.biopha.2021.111961

Abstract

We previously reported the anticancer activity of 4-(4-fluorobenzylcarbamoylmethyl)-3-(4-cyclohexylphenyl)-2-[3-(N,N-dimethylureido)-N'-methylpropylamino]-3,4-dihydroquinazoline (OZ-001), a T-type calcium channel (TTCC) blocker, against non-small cell lung cancer (NSCLC) in vitro and in vivo. Here, we evaluated the synergistic effect of OZ-001 and cisplatin on A549 human lung cancer cells and A549 xenograft mice. Our study demonstrated that treatment with OZ-001 and cisplatin sensitized A549 cells to cisplatin and significantly inhibited cell growth, increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and induced poly (ADP-ribose) polymerase (PARP) cleavage in A549 cells and an A549 xenograft tumor mouse model. Moreover, our findings showed that mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and signal transducer and activator of transcription (STAT3) inactivation was required for apoptosis induced by the combination of OZ-001 and cisplatin in in vitro and in vivo experiments. Our results suggest that combined treatment with OZ-001 and cisplatin could potentiate antiproliferative effects via suppression of the mTOR/p70S6K and STAT3 pathways and may be considered a potential therapeutic agent for NSCLC.

Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Keywords: Apoptosis; Combined therapy; Non-small cell lung cancer; OZ-001; P70S6K

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