Table 2. Preclinical studies in primary effusion lymphoma targeting the proteasome and/or the NF-κB pathway.
| Study | Agent | Activity | Model | Key findings |
|---|---|---|---|---|
| El Hajj et al.69 | Combination of arsenic trioxide and IFN-α | NF-κB inhibition; antiviral activity | In vitro: PEL cell lines; in vivo: xenograft mouse model | Dramatic inhibition of proliferation, induction of apoptosis and downregulation of the latent viral transcripts LANA-1, v-FLIP and v-Cyc; decrease in the peritoneal volume and prolonged survival of PEL mice |
| Bhatt et al.63 | Proteasome/HDAC inhibitor | Proteasome and NF-κB inhibition; histone deacetylase inhibition | In vivo: xenograft mouse model | Extensive apoptosis and significant survival advantage in PEL-bearing mice |
| Goto et al.54 | Berberine (isoquinoline alkaloid) | NF-κB inhibition | In vitro: PEL cell lines; in vivo: xenograft mouse model | Cell death by blocking the NF-κB pathway in PEL cells; antiretroviral activity |
| Matsuno et al.37 | Diethyldithio-carbamate (DDTC) | NF-κB inhibition | In vivo: xenograft mouse model | Amelioration of PEL symptoms |
| Higashi et al.56 | Heat-shock protein 90 inhibitors | NF-κB inhibition | In vitro: PEL cell lines | Induction of apoptosis in PEL cell lines |
| Saji et al.62 | MG132, lactacystin, proteasome inh 1 | Proteasome and NF-κB inhibition | In vitro: PEL cell lines | Inhibition of proliferation and induction of apoptosis in PEL cells |
| Sarosiek et al.16 | Bortezomib | Proteasome and NF-κB inhibition | In vivo: xenograft mouse model | PEL remission and increase of overall survival in PEL-treated mice |
| Hussain et al.53 | Proteasome inhibitor: MG-132 | Proteasome and NF-κB inhibition | In vitro: PEL cell lines | Apoptosis of PEL cells via downregulation of SKP2 leading to accumulation of p27Kip1 |
| Takahashi et al.55 | Biscoclaurine alkaloid cepharanthine (CEP) | NF-κB inhibition | In vitro: PEL cell lines; In vivo: xenograft mouse model | No significant systemic toxicity in this model; dose-dependent inhibition of proliferation and apoptosis of PEL cell lines |
| Abou-Merhi et al.61 | Bortezomib; combination of arsenic and IFN-α | Proteasome and NF-κB inhibition | In vitro: PEL cell lines | Dramatic inhibition of cell proliferation and induction of apoptosis |
| Matta et al.52 | Bortezomib | Proteasome and NF-κB inhibition | In vitro: PEL cell lines | More cytotoxicity against PEL cells than against cell lines derived from multiple myeloma |
| An et al.60 | Bortezomib ±chemotherapy (doxorubicin and taxol) | Proteasome and NF-κB inhibition | In vitro: PEL cell lines | TRAIL-induced death, inhibition of cell growth and induction of apoptosis in PEL cells; synergy with chemotherapy |
Abbreviations: HDAC, histone deacetylase; IFN-α, interferon-alpha; NF-κB, nuclear factor kappa B; PEL, primary effusion lymphoma; TRAIL, tumor necrosis factor-related apoptosis inducing ligand.