Table 3.
The anti-cancer effects of combination treatment of retinoids and other drugs
| Cancer type | Retinoids (concentration) | Combined drug (concentration) | Study Model | Findings | References |
|---|---|---|---|---|---|
| Breast cancer | All-trans-RA (10 μM) | Epirubicin (20 μM) | MCF7 cells (In vitro) | ● Inhibited cell migration and invasion (stronger than epirubicin) | [57] |
| ● Up-regulated GRIM-19 and down-regulated STAT3 in the JAK/STAT signaling pathway | |||||
| All-trans-RA (5 μM) | Docosahexaenoic acid (30 μM) | ● Induced apoptosis (stronger than all-trans-RA) | [59] | ||
| All-trans-RA (0.75 μM) | Interferon-β (1.87 μM) | ● Inhibited cell proliferation and migration | [58] | ||
| Curcumin (40 μM) | ● Induced apoptosis | ||||
| All-trans-RA (20 μM) | ω-3 free fatty acids (80 μM) | ER + MCF7 and HER2 + SKBR3 cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [60] | |
| ● Induced apoptosis | |||||
| All-trans-RA (10 μM) | Trastuzumab (0.0687 μM) | BT474 and SKBR3 cells (In vitro) | ● Inhibited cell proliferation, invasion, and migration (stronger than all-trans-RA) | [50] | |
| ● Down-regulated FAK and HER2 in their respective signaling pathways | |||||
| Melanoma | All-trans-RA (17.53 μM) | Allicin (30.81 μM) | CD44+ cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [54] |
| ● Up-regulated MMP-9 in the EGFR/MAPK signaling pathway, cyclin D1 in the Wnt/β-catenin signaling pathway, and RAR in the RAR/RXR signaling pathway | |||||
| All-trans-RA (12.65 μM) | CD20 antibody (1 μg/mL) | CD20 + cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [64] | |
| All-trans-RA (5 μM) | Paclitaxel (0.005 and 0.01 μM) | A375 cells (In vitro) | ● Inhibited cell proliferation (stronger than paclitaxel) | [62] | |
| All-trans-RA | Vorinostat | A375, HL60, LN229, L929, SH-SY5Y and U-118 MG cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [63] | |
| (In combination: 12.5 and 25 μM) | ● Induced apoptosis | ||||
| All-trans-RA | Vorinostat | Xenograft tumor mice (In vivo) | ● Suppressed tumor development | ||
| (In combination: 10 mmol/kg (body weight)) | |||||
| All-trans-RA (150 mg/m2) | Ipilimumab (10 mg/kg) | Phase II human clinical trial | ● Decreased the frequency of circulating myeloid-derived suppressor cells | [65] | |
| ● Suppressed the frequency of occurrence for Grade 3 or 4 adverse effects | |||||
| Colorectal cancer | All-trans-RA | Oxaliplatin | SW-480 cells (In vitro) | ● Inhibited cell proliferation | [67] |
| (Nanoparticles: 5 μg/mL) | ● Induced apoptosis | ||||
| Hepatocellular carcinoma | All-trans-RA (10 μM) | Interferon-β (4.99 μM) | HepG2 cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA and interferon-β) | [69] |
| ● Induced apoptosis | |||||
| ● Down-regulated JAK2 and STAT3 in the JAK/STAT signaling pathway | |||||
| All-trans-RA | Paclitaxel | A549 cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [70] | |
| (In combination: 25.7 μM) | |||||
| All-trans-RA (0.35 mg/kg (body weight)) | Paclitaxel (2 mg/kg (body weight)) | Xenograft tumor mice (In vivo) | ● Suppressed tumor development | ||
| ● Prolonged survival rate | |||||
| Neuroblastoma | All-trans-RA (5 μM) | Estradiol (0.001 μM) | SH-SY5Y cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [74] |
| Cholesterol (12.93 μM) | |||||
| All-trans-RA (0.1 μM) | NaB (1000 μM) | SH-SY5Y and SK-N-BE cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [53] | |
| 5-Aza (1 μM) | ● Up-regulated RAR in the RAR/RXR signaling pathway | ||||
| All-trans-RA (0.1 μM) | TNIIIA2 (3 μg/mL) | IMR-32 and Kelly cells (In vitro) | ● Accelerated cell differentiation (stronger than all-trans-RA and TNIIIA2) | [75] | |
| ● Down-regulated N-Myc in the MYCN signaling pathway | |||||
| All-trans-RA (6.67 mg/kg (body weight)) | TNIIIA2 (8.34 mg/kg (body weight)) | Xenograft tumor mice (In vivo) | ● Suppressed tumor development (stronger than all-trans-RA) | ||
| 13-cis-RA (50 μM) | Poly (I:C) (50 μg/ml) | SK-N-DZ cells (In vitro) | ● Inhibited cell proliferation (stronger than 13-cis-RA) | [45] | |
| ● Induced apoptosis | |||||
| ● Up-regulated mitochondrial stress response | |||||
| 13-cis-RA (5 mg/kg (body weight)) | Poly (I:C) (10 mg/kg (body weight)) | Xenograft tumor mice (In vivo) | ● Suppressed tumor development through acceleration in neural differentiation and inhibition of vessel formation | ||
| Cutaneous T-cell lymphoma | Tamibarotene (25 μM) | MS-275 (1 μM) | SeAx cells (In vitro) | ● Inhibited cell proliferation (stronger than tamibarotene) | [39] |
| ● Up-regulated RAR in the RAR/RXR signaling pathway | |||||
| Tamibarotene (2 mg/kg (body weight)) | MS-275 (5 mg/kg (body weight)) | Xenograft tumor mice (In vivo) | ● Suppressed tumor development (stronger than tamibarotene) | ||
| ● Prolonged survival rate | |||||
| Glioma | All-trans-RA (10 μM) | Temozolomide (400 μM) | U251 cells (In vitro) | ● Inhibited cell proliferation (stronger than temozolomide) | [19] |
| ● Induced apoptosis | |||||
| ● Inhibited the Keap1/Nrf2/ARE signaling pathway | |||||
| 9-cis-RA (600 μM) | Metformin (20000 μM) | C6 cells (In vitro) | ● Induced apoptosis (stronger than 9-cis-RA or metformin) | [78] | |
| ● Up-regulated caspase-3 in the caspase signal pathway | |||||
| Lung cancer | All-trans-RA (10 μM) | Gefitinib (15 μM) | A549 and H1650 cells (In vitro) | ● Inhibited cell proliferation (stronger than gefitinib) | [79] |
| All-trans-RA (0.01 μM) | CIK cells | A549 and NCI-H520 cells (In vitro) | ● Inhibited cell proliferation | [47] | |
| Effector: Target ratio of CIK cells | ● Down-regulated BCL-2 and surviving, and up-regulated BAX in the caspase signaling pathway | ||||
| (20:1) | |||||
| Gastric cancer | All-trans-RA (25 μM) | DAPT (5 μM) | AGS and MKN45 cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [80] |
| ● Up-regulated caspase-3 in the caspase signaling pathway | |||||
| All-trans-RA | Podophyllotoxin | MKN45 and BGC-823 cells (In vitro) | ● Inhibited cell proliferation (stronger than all-trans-RA) | [49] | |
| ● Induced apoptosis | |||||
| (Conjugate: 0.5 μM) | ● Up-regulated RAR in the RAR/RXR signaling pathway and down-regulated ERK1/2 and AKT in the PI3K/AKT signaling pathway | ||||
| Thyroid cancer | All-trans-RA (70 μM) | Sorafenib (18 μM) | FTC-133 cells (In vitro) | ● Inhibited cell proliferation | [83] |
| ● Down-regulated ERK2 in the ERK/MAPK signaling pathway | |||||
| All-trans-RA | Sorafenib | BALB/c nude mice (In vivo) | ● Induced apoptosis | ||
| (Polymer micelles: 10 mg/kg (body weight)) | ● Induced re-differentiation of cells in tumor tissue | ||||
| 13-cis-RA (1.5 mg/kg) | Iodine-131 (60 μg) | Human clinal trial | ● Reduced or stabilized tumor size after 2.5 years | [82] | |
| Pancreatic cancer | All-trans-RA (50 μM) | Gemcitabine (10 μM) | AsPC-1 cells (In vitro) | ● Inhibited cell proliferation (stronger than gemcitabine) | [24] |
| All-trans-RA (30 μM) | Gemcitabine 0.6 μM | MiaPaCa-2 and TB33117 cells (In vitro) | ● Inhibited cell proliferation and migration (stronger than gemcitabine) | [84] | |
| ● Down-regulated PAK in the PAK signaling pathway | |||||
| All-trans-RA (45 mg/m2) | Paclitaxel (125 mg/m2) | Phase I human clinical trial | ● Grade 4 of Dose-Limiting Toxicity | [85] | |
| ● Achieved survival duration of 11.7 months | |||||