Tanshinone IIA enhances susceptibility of non-small cell lung cancer cells to NK cell-mediated lysis by up-regulating ULBP1 and DR5.


Journal

Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628

Informations de publication

Date de publication:
08 2021
Historique:
revised: 08 04 2021
received: 24 11 2021
accepted: 09 04 2021
pubmed: 29 4 2021
medline: 31 8 2021
entrez: 28 4 2021
Statut: ppublish

Résumé

Natural killer (NK) cells have a great potential in cancer immunotherapy. However, their therapeutic efficacy is clinically limited owing to cancer cell immune escape. Therefore, it is urgently necessary to develop novel method to improve the antitumor immunity of NK cells. In the present study, it was found that the natural product tanshinone IIA (TIIA) enhanced NK cell-mediated killing of non-small cell lung cancer (NSCLC) cells. TIIA in combination with adoptive transfer of NK cells synergistically suppressed the tumor growth of NSCLC cells in an immune-incompetent mouse model. Furthermore, TIIA significantly inhibited the tumor growth of Lewis lung cancer (LLC) in an immune-competent syngeneic mouse model, and such inhibitory effect was reversed by the depletion of NK cells. Moreover, TIIA increased expressions of ULBP1 and DR5 in NSCLC cells, and inhibition of DR5 and ULBP1 reduced the enhancement of NK cell-mediated lysis by TIIA. Besides, TIIA increased the levels of p-PERK, ATF4 and CHOP. Knockdown of ATF4 completely reversed the up-regulation of ULBP1 and DR5 by TIIA in all detected NSCLC cells, while knockdown of CHOP only partly reduced these enhanced expressions in small parts of NSCLC cells. These results demonstrated that TIIA could increase the susceptibility of NSCLC cells to NK cell-mediated lysis by up-regulating ULBP1 and DR5, suggesting that TIIA had a promising potential in cancer immunotherapy, especially in NK cell-based cancer immunotherapy.

Identifiants

pubmed: 33909909
doi: 10.1002/JLB.5MA1120-776RR
doi:

Substances chimiques

Abietanes 0
Antineoplastic Agents, Phytogenic 0
Biomarkers 0
GPI-Linked Proteins 0
Intracellular Signaling Peptides and Proteins 0
Receptors, TNF-Related Apoptosis-Inducing Ligand 0
TNFRSF10B protein, human 0
ULBP1 protein, human 0
tanshinone 03UUH3J385

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

315-325

Informations de copyright

©2021 Society for Leukocyte Biology.

Références

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Auteurs

Yufang Sun (Y)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Chenyuan Gong (C)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Zhongya Ni (Z)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Dan Hu (D)

School of Acupuncture, Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Wanyi Ng (W)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Xiaowen Zhu (X)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Lixin Wang (L)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Guifan Si (G)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Xuewei Yan (X)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Chen Zhao (C)

School of Acupuncture, Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Chao Yao (C)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

Shiguo Zhu (S)

Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.

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Classifications MeSH