Table 1 Table summarizes main basic studies assessing the role of proteasome inhibitors in NPC tissue samples, cell lines, xenografts and murine models
Study | Cell lines | Patient Samples / animal studies | Treatment | Endpoints or objectives | Outcomes/Results |
|---|---|---|---|---|---|
Li et al. [36] | CNE1, CNE-LMP1+ | – | MG-132 | Study of LMP1 regulating the expression of MDM2 | MDM2 expression is upregulated by LMP1 through a post-ubiquitination mechanism. |
Hau et al. [38] | HONE1, HONE1-EBV, CNE2-EBV C666–1, NP460-hTERT | – | MG-132 | Examination of LMP1 protein levels in different EBV-infected cell lines | - LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. - Binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells. -Proteasome inhibitor could effectively stabilize LMP1 protein in EBV-infected cells - Id1 could interact and stabilize LMP1 by suppressing LMP1 polyubiquitination. |
Gainullin et al. [39] | CNE1, CNE2, TWO3, HONE1 | 9 NPC tissues 10 normal epithelial tissues from chronic nasopharyngitis patients | MG-132 | Role of LMP2A in the accumulation of cofilin in NPC. | - LMP2A was found to interfere with cofilin degradation in NPC cells by accelerating the proteasomal degradation of Cbl and Syk. - Interference with cofilin degradation may enhance the metastatic potential of NPC cells |
Zhou et al. [40] | HONE1/Akata, HK1/Akata, C666–1, CNE1/Akata, CNE1 (EBV-) | 43 NPC tissues PBMCs BALB/c nude mice | Triptolide MG-132 | Anti-cancer effect of triptolide and mechanism of EBNA1 in NPC cells | Low dose of triptolide reduce the half-life of EBNA1 and significantly decreased EBNA1 expression by promoting the process of proteasome ubiquitin pathway. |
Zhang et al. [22] | CNE1, CNE2, HNE1, HONE1, HK1, SUNE1, C666–1, NPEC2-Tert, NPEC5-Tert Primary NPC cell lines | – | – | Interplay between EBV gB and host proteins | - FBXO2 ubiquitinates and degrades glycosylated gB. - Identification of SCFFBXO2 as an E3 ubiquitin ligase targeting EBV envelope protein gB. |
Meng et al. [41] | CNE1, CNE2 (S18, S26), SUNE-1 (5–8) | 50 NPC tissues | MG132 | Molecular mechanisms of NPC metastasis | - S100A14 promoted the ubiquitin-proteasome-mediated degradation ofIRAK1 to suppress NPC cellular migration. - Lower S100A14 expression was significantly correlated with shorter patient OS and DMFS. |
Pan et al. [42] | CNE1, CNE2, HONE1, C666.1 | 45 NPC tissues 30 control | LLnL MG132 LLM | Functional relationship between Jab1 and p27 protein expression | - Jab1-mediated p27 degradation in a proteasome-dependent manner. - Overexpression of Jab1 correlated with poor survival in NPC patients. |
Liu et al. [43] | HONE1 HK1 | – | Curcumin MG-132 | Effect of curcumin on the proliferation, cycle arrest, and apoptosis of EBV+ NPC cells | Curcumin induced EBNA1 degradation via the proteasome-ubiquitin pathway |
Friboulet et al. [44] | C666–1 CNE2 (EBV-) | 13 NPC biopsies C15 and C17 (EBV+ in nude mice) NPC xenografts | MG132 Epoxomicin | Functions of c-IAP2 in NPC cells | - RMT 5265 induces the proteasome-mediated degradation of c-IAP2, resulting from the enhanced polyubiquitination of c-IAP2 |
Hui et al. [45] | HONE1, HK1-EBV, HONE1-EBV, HA, C666–1 | Female BALB/c nude (nu/nu) mice | Bortezomib, SAHA (Vorinostat) | Mechanisms of apoptosis and effects on lytic cycle activation of EBV | - Combination of bortezomib and SAHA synergistically induce killing of a panel of NPC cell lines and suppresses the growth of NPC xenografts in nude mice. - Bortezomib inhibits SAHA’s induction of EBV replication and abrogates production of infectious viral particles in NPC cells. |
Xu C. et al. [46] | NP69, CNE2, Hone1, C666–1 |  | MG132 | Mechanisms by which EBV elude immune responses | - LMP1 inhibits Sendai virus mediated type I interferon production and downregulates RIG-I signaling pathway by promotion RIG-I degradation dependent on proteasome. - EBV employs a unique strategy to evade RIG-I mediated immune responses. |
Jiang et al. [44] | CNE2, CNE1 |  | Bortezomib (PS-341) | Mechanism by which immune evasion affects the response to treatment of NPC. | - Bortezomib downregulates IFNγ-induced IDO expression via inhibition of JAK/STAT1 signaling pathway. - Bortezomib can promote IkB-α phosphorylation-ubiquitination to release NF-kB from IkB-α. |