Table 1.
In vitro radiobiology studies conducted using 3D models (spheroid-based and substrate-based) of breast cancer tissues.
| S No | Cells Matrix (Substrate-Based) |
Radiation Dosage | Dose Rate | Observations (Radiation Effects) | Methods of Analysis | Ref. |
|---|---|---|---|---|---|---|
| Irradiator | ||||||
| Spheroid-Based Models | ||||||
| 1 | MDA-MB-231, SUM1315 | 2 Gy x 5 | 400 (MU/min) | Radiosensitizer: Olaparib in low doses with longer exposure team enhances radiosensitivity | Metabolic activity, live/dead analysis | [105] |
| Varian Medical Systems | ||||||
| 2 | MCF-7, primary human breast cancer | 2, 4, 6 Gy | Radiosensitizer: Valproic acid radiosensitizes in 2D and radioprotects in 3D | GelCount Colony Counter | [106] | |
| Cs-137 irradiator | ||||||
| 3 | GFP-4T1 + 2H11 murine endothelial cells | 2 Gy | Co-culture: Presence of endothelial cells sensitized cells to chemotherapy and protected tumor cells from irradiation | 2D replating and survival assay | [111] | |
| Not stated | ||||||
| 4 | SUM159PT, MDA-MB-231 | 4, 8 Gy | 2.789 Gy/min | Radiosensitizer: Mebendazole inhibited IR-induced conversion of TNBC cells into cancer-initiating phenotype | Mammospheres count | [46] |
| X-ray irradiator Gulmay Medical Inc | ||||||
| 5 | T47D, HTB-133, MDA-MB-361, MDA-MB-231 + primary normal human dermal fibroblasts | 2, 4, 6, 8 Gy | 0.5 Gy/min | Radiosensitizer and co-culture: Vinblastine and radiation inhibited cancer cell growth | Image-based analysis of tissue area | [107] |
| Cs-137 irradiator | ||||||
| 6 | T47D, JIMT-1 | 5 Gy | 0.95 Gy/minute | Radiosensitizer: Trastuzumab and radiation inhibited growth in 3D | Image-based analysis of tissue area | [108] |
| Cs-137 irradiator | ||||||
| 7 | 4T1-mCherry tumor cells, C166-GFP endothelial cells, murine embryonic fibroblasts | 3 Gy | 1.018 ± 0.10 Gy/min | Radiation enhances expression of Galectin-1 in endothelial cells that is targeted using nanoparticles carrying arsenic trioxide and cisplatin | Dead cell staining (Sytox blue) | [110] |
| Varian TrueBeam System | ||||||
| 8 | MCF-7 | 2, 4, 6, 8 Gy | 200 MU/min | Increased radiosensitivity in 3D compared to 2D Curcumin enhances radiosensitivity of cancer cells |
MTT assay, RT-PCR, ELISA | [102] |
| PRIMUSTM linear accelerator | ||||||
| 9 | A549 lung adenocarcinoma, DU-145 and PC-3 prostate cancer and MCF-7 breast cancer | 0, 2, 4 Gy | Radiosensitizer: Gold nanoparticle, Vorinostat and radiation reduces colony forming ability of cells and enhanced DNA damage | 2D replating and clonogenic survival assay, γH2AX staining | [109] | |
| Primus linear accelerator | ||||||
| Substrate-based Models | ||||||
| 10 | MCF7, MDA-MB-231, SK-BR-3 Matrigel |
2, 6 Gy | Gene expression of CSC depended on radiation dose Radiation had differing effects on expression of MMP, TIMP and HDAc |
RT-PCR | [136] | |
| Yxlon Smart Maxishot 200-E | ||||||
| 11 | T4-2 (malignant) GFR BME (laminin-rich ECM) |
2, 4 Gy | IR caused upregulation of integrin leading to increased cell survival Inhibition of integrin induced apoptosis |
Immunoblotting, immunofluorescence, TUNEL assay | [90] | |
| Not stated | ||||||
| 12 | 184A1 human MamECs Matrigel |
0.5, 1, 2.5, 5 Gy | 0.16–0.58 Gy/min | Reduced apoptosis in 3D compared to 2D Increased survival in long-term 3D cultures because of growth inhibition in 3D |
Trypsinize and count, flow cytometry | [104] |
| Pantak XRAD 320 Cabinet X-ray machine | ||||||
| 13 | MCF10a, 184v human MamECs Matrigel |
0.4–2 Gy | X-ray: 4 Gy/min, 0.03 Gy/min γ: 0.03–2 Gy/min, 56Fe: 0.2–1 Gy/min |
E-cadherin was reduced in TGF-β–treated cells irradiated with radiation TGF-β–mediated EMT is not dependent on radiation dose or quality |
Immunofluorescence (cryosections) | [137] |
| X-rays: Varian 2300 linear accelerator | ||||||
| 14 | T4-2 (malignant), S1 (non-malignant) GFR BME (laminin-rich ECM) |
0–8 Gy | Integrin induced by exposure to radiation through NFkB–mediated gene activation in 3D | Western blot, RT-PCR, NF-kB DNA-binding assay, immunofluorescence, TUNEL assay | [89] | |
| Not stated | ||||||
| 15 | A549 adenocarcinoma, MCF7, PC3 prostate cancer Matrigel |
0–4 Gy | 0.751 Gy/min | 3D cultures have increased radioresistance | 2D replating and survival assay | [103] |
| Faxitron RX-650 facility | ||||||
| 16 | Py8119, NIH-3T3 Matrigel |
3, 6, 9 Gy | 3 Gy/min | Co-culture: Presence of fibroblasts increased the survival fraction of irradiated cultures | Survival assay and fluorescence | [49] |
| Isovolt-320-X-ray machine | ||||||
| 17 | MCF10A, MCF7 Matrigel |
0.5, 2, 4, 6 Gy | 3.75 Gy/min | Radiosensitizer: Simvastatin tends to radiosensitize in 2D and not in 3D | 3D clonogenic survival assay | [92] |
| Linac Siemens Oncor Expression | ||||||
| Not stated | ||||||
MU/min: Monitor Units per minute; Cs-137: Caesium-137; GFP: Green Fluorescent Protein; IR: Irradiation; TNBC: Triple-negative breast cancer; MTT: 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide; RT-PCR: Real Time polymerase chain reaction; ELISA: Enzyme-Linked Immunosorbent Assay; γH2AX: gamma Histone-2AX; CSC: Cancer Stem Cells; MMP: Matrix metalloproteinases; TIMP: The tissue inhibitors of metalloproteinases; HDAc: Histone deacetylase; GFR: Growth Factor Reduced; BME: basement membrane extract; ECM: Extracellular Matrix; TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling; MamECs: mammary epithelial cells; TGF-β: Transforming growth factor beta; EMT: Epithelial to Mesenchymal transition; NFkB: Nuclear Factor kappa-light-chain-enhancer of activated B cells; DNA: Deoxyribonucleic acid.