Table 1.
Performance of GSIs in preclinical models.
| GSIs | Cancer Types | Intervention objects | Effect | Reference |
|---|---|---|---|---|
| GSI and LY-411,575 | Kaposi's sarcoma | Kaposi's sarcoma tumor cells | Induction of apoptosis | PMID: 15940249 91 |
| GSI-XII (Z-IL-CHO) and GSI-IX (DAPT) | Multiple myeloma | NCI-H929, U266 and RPMI-8226 | Induction of apoptosis | PMID: 21965140 92 |
| Z-LLNle-CHO | Breast cancer | MCF-7, BT474, T47D, SKBR3, MDA-MB-231, and MDA-MB-468 | Z-LLNle-CHO mediates the damage to breast cancer cells through proteasome inhibition (rather than γ -secretase inhibition) | PMID: 19660128 93 |
| LLNle | Glioblastoma | human glioblastoma tumor-initiating cells (GBM TICs) | LLNle mediates the GBM TICs apoptotic cell death through γ-secretase and proteasome inhibition | PMID: 19861404 94 |
| MRK-003 | Pancreatic cancer | Pa03C, Pa14C, Pa16C and Pa29C; patient-derived PDAC xenografts | MRK-003 can reduce tumor cell proliferation, induce apoptosis and intratumoral necrosis | PMID: 22752426 95 |
| DAPT | Ovarian cancer | SKOV3 and HO8910 | DAPT prevents ovarian cancer stem cells (OCSCs) formation, and inhibits OCSC self-renewal and proliferation | PMID: 23482909 96 |
| RO4929097 | Melanoma | WM35, WM98.1, WM115, WM983A, WM3248, A375, WM239A/131/4-5B1 (5B1); human primary melanoma xenograft in NOD/SCID/IL2gammaR-/- mice | RO4929097 can weaken cell proliferation and tumor growth of Melanoma. | PMID: 21980408 97 |
| MRK-003, MRK-006 | T-cell acute lymphoblastic leukemias (T-ALL) | T-All cells | Combination of GSI with a CDK4 inhibitor results in potent cell cycle arrest and death. | PMID: 19318552 98 |
| RO4929097 | NSCLC | A549, H460a cells, A549 NSCLC xenograft model | Significant tumor growth inhibition | PMID: 19773430 99 |
| PF-03084014 | Prostate Cancer | Du145, PC3 and Du145R, PC3R; 7-8-week-old male NOD.CB17-Prkdcscid/NCrCrl (NOD/SCID) mice | PF-03084014 enhanced the docetaxel-mediated tumor response | PMID: 26202948 100 |
| MK-0725 | Ovarian cancer | A2780, OVCAR3, SKOV3, HO8910PM; Mouse xenograft model of A2780 | Induction of apoptosis; Significant tumor growth inhibition | PMID: 26704638 101 |
| GSI I and GSI XX | NSCLC | H460, A549 and H1395 | Treatment with GSIs after radiation can significantly enhance radiation-mediated tumour cytotoxicity and delay tumor progression. | PMID: 22596234 102 |
| DAPT | Ovarian cancer | A2780, A2780/CP70 and OV2008, OV2008/C13 | DAPT pretreatment can improve the sensitivity of cisplatin-resistant human ovarian cancer cells to cisplatin. | PMID: 24535252 103 |
| BMS-708163 | Lung Cancer | PC9, PC9/AB2, PC9/AB2 xenografts | BMS-708163 can sensitize PC9/AB2 cells to gefitinib-induced cytotoxicity. BMS-708163 combined with gefitinib can induce high level of apoptosis. And the combination of gefitinib and BMS-708163 can inhibit the growth of PC9/AB2 xenografts. | PMID: 25561332 104 |
| GSI I (cbz-IL-CHO) | Gastric cancer | AGS, SNU601, SNU638, SNU-668, SNU-719, MKN28, and YCC-2; orthotopically transplanted gastric cancer mouse models | GSI I can significantly inhibit the proliferation of gastric cancer cells and reduce the tumor load of orthotopic transplantation mouse models, and the combination of GSI I and 5-FU can enhance the therapeutic effect | PMID: 26134677 105 |