Sema4D silencing increases the sensitivity of nivolumab to B16-F10 resistant melanoma via inhibiting the PI3K/AKT signaling pathway

被引:2
作者
Zhang, Zhuo [1 ,2 ]
Zhang, Duoli [2 ]
Wang, Fang [1 ,2 ]
Liu, Jiao [3 ]
Sun, Yuhong [2 ]
Anuchapreeda, Songyot [1 ]
Tima, Singkome [1 ]
Xiao, Zhangang [2 ]
Duangmano, Suwit [1 ]
机构
[1] Chiang Mai Univ, Fac Associated Med Sci, Dept Med Technol, Chiang Mai, Thailand
[2] Southwest Med Univ, Sch Pharm, Dept Pharmacol, Luzhou, Peoples R China
[3] Southwest Med Univ, Dept Pharm, Affiliated Hosp, Luzhou, Peoples R China
来源
PEERJ | 2023年 / 11卷
关键词
Sema4D; Melanoma; Nivolumab; PI3K; AKT; PD-1 inhibitor resistance; IPILIMUMAB; PEMBROLIZUMAB; CHEMOTHERAPY; MECHANISMS; BLOCKADE; THERAPY; CANCER; PD-1;
D O I
10.7717/peerj.15172
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Melanoma is a common skin tumor that causes a high rate of mortality, especially in Europe, North America and Oceania. Immunosuppressants such as anti-PD-1 have been used in the treatment of malignant melanoma, however, nearly 60% of patients do not respond to these treatments. Sema4D, also called CD100, is expressed in T cells and tumor tissues. Sema4D and its receptor, Plexin-B1, play crucial roles in the process of immune regulation, angiogenesis, and tumor progression. The role of Sema4D in melanoma with anti-PD-1 resistance is poorly understood. Through a combination of molecular biology techniques and in silico analysis, the role of Sema4D in improving anti-PD-L1 sensitivity in melanoma was explored. The results showed that the expression of Sema4D, Plexin-B1 and PD-L1 was significantly increased in B16-F10R cells. Sema4D knockdown synergizes with anti-PD-1 treatment, cell viability, cell invasion and migration were significantly decreased, while the apoptosis was increased, the growth of tumors on the mice was also inhibited. Mechanistically, bioinformatics analysis revealed that Sema4D is involved in the PI3K/AKT signaling pathway; the downregulation of p-PI3K/PI3K and p-AKT/AKT expression were observed in Sema4D knockdown, therefore, nivolumab resistance is related to Sema4D and Sema4D silencing can improve sensitivity to nivolumab via inhibition of the PI3K/AKT signaling pathway.
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页数:20
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共 42 条
  • [1] Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma
    Algazi, Alain P.
    Twitty, Christopher G.
    Tsai, Katy K.
    Le, Mai
    Pierce, Robert
    Browning, Erica
    Hermiz, Reneta
    Canton, David A.
    Bannavong, Donna
    Oglesby, Arielle
    Francisco, Murray
    Fong, Lawrence
    Pittet, Mikael J.
    Arlauckas, Sean P.
    Garris, Christopher
    Levine, Lauren P.
    Bifulco, Carlos
    Ballesteros-Merino, Carmen
    Bhatia, Shailender
    Gargosky, Sharron
    Andtbacka, Robert H. I.
    Fox, Bernard A.
    Rosenblum, Michael D.
    Daud, Adil I.
    [J]. CLINICAL CANCER RESEARCH, 2020, 26 (12) : 2827 - 2837
  • [2] Tumor Microenvironment
    Arneth, Borros
    [J]. MEDICINA-LITHUANIA, 2020, 56 (01):
  • [3] CD3ζ based chimeric antigen receptors mediate T cell activation via cis-and trans-signalling mechanisms: implications for optimization of receptor structure for adoptive cell therapy
    Bridgeman, J. S.
    Ladell, K.
    Sheard, V. E.
    Miners, K.
    Hawkins, R. E.
    Price, D. A.
    Gilham, D. E.
    [J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2014, 175 (02) : 258 - 267
  • [4] Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers
    Bronte, V
    Kasic, T
    Gri, G
    Gallana, K
    Borsellino, G
    Marigo, I
    Battistini, L
    Iafrate, M
    Prayer-Galetti, T
    Pagano, F
    Viola, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (08) : 1257 - 1268
  • [5] Roles of Sema4D and Plexin-B1 in tumor progression
    Ch'ng, Ewe Seng
    Kumanogoh, Atsushi
    [J]. MOLECULAR CANCER, 2010, 9
  • [6] Photothermal effect by 808-nm laser irradiation of melanin: a proof-of-concept study of photothermal therapy using B16-F10 melanotic melanoma growing in BALB/c mice
    Colombo, Lucas L.
    Vanzulli, Silvia, I
    Blazquez-Castro, Alfonso
    Sanchez Terrero, Clara
    Stockert, Juan C.
    [J]. BIOMEDICAL OPTICS EXPRESS, 2019, 10 (06) : 2932 - 2941
  • [7] The Role of the PI3K-AKT Pathway in Melanoma
    Davies, Michael A.
    [J]. CANCER JOURNAL, 2012, 18 (02) : 142 - 147
  • [8] Cutaneous melanoma
    Eggermont, Alexander M. M.
    Spatz, Alan
    Robert, Caroline
    [J]. LANCET, 2014, 383 (9919) : 816 - 827
  • [9] Hirano F, 2005, CANCER RES, V65, P1089
  • [10] A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance
    Huang, Alexander C.
    Zappasodi, Roberta
    [J]. NATURE IMMUNOLOGY, 2022, 23 (05) : 660 - 670