Table 1 Effects of some drugs and cancer cell mechanisms of drug resistance in monolayer and in three-dimensional cell cultures
From: The multiple facets of drug resistance: one history, different approaches
Drug | Cell type | Effects in 2D and 3D cultures | Processes related to chemoresistance | Reference |
|---|---|---|---|---|
Doxorubicin/Paclitaxel/Tamoxifen/ | MCF-7 (breast carcinoma) | Antiproliferative effect increased in 2D; cells more resistant to drugs in 3D. | Increased ECM production in 3D models, difficulting drug diffusion. | Horning et al.[143] |
AG1478 | SW-480, HT-29, DLD-1, LOVO, CACO-2. COLO-205, COLO-206F (Colorectal Cancer Cell Lines) | Cell viability decreased in a dose-dependent way in 2D and 3D, but more clearly in 2D. | Cells in 3D showed decreased expression of EGFR. ECM signaling can be involved too. | Luca et al.[98] |
5FU/ Docetaxel/ Cisplatin/Carboplatin | SKOV-3 cell line (epithelial ovarian cancer). Stem cells were selected from these cultures. | Antiproliferative effect increased in 2D. Cells in 3D models more resistant to drugs. | Decreased apoptotic induction in 3D. Increased expression of ABCG2 e ABCB1 in 3D. | Chen et al.[116] |
Paclitaxel | SKOV-3 (epithelial ovarian cancer) | Increased expression of KLK4 favors multicellular aggregates formation and these are more resistant to drug. | Increased expression of KLK4. | Dong et al.[115] |
Doxorubicin/ Cisplatin | SW1353, CH2879, JJ012, OUMS27 (chondrosarcoma cell lines) | In 3D models doxorubicin can reach cell’s nuclei but cells are more resistant to the drug. | Drug penetration is not dependent on MDR activity. Bcl-2 members are important to resistance. | Van Oosterwijk et al.[29] |
Taxol/Cisplatin | HEY, A2780, SKOV3, OVAC429 (human ovarian cancer) | Cells cultured in 3D are more resistant to taxol treatment. | Cells from some cell lines did not arrested in G2-M after taxol treatment. | Frankel et al.[144] |
Doxorubicin | HepG2 (human hepatocellular liver carcinoma) and 3T3-J2 (fibroblasts murine stromal cells) | Increased cell viability in 3D. 3D heterospheroids are more resistant than 2D and homospheroid models. | Stromal fibroblasts and collagen hydrogel culture system provides more resistance. | Yip & Cho [105] |
Doxorubicin | HT1080 (human fibrosarcoma) | In 2D doxorubicin decreased cell migration, and in 3D the drug did not affeted cell migration. | EMC proteins in a 3D configuration are able to protect cancer cells from the antimigratory effect of doxorrubicin. Environment-mediated drug resistance. | Millerot-Serrurot [106] |
Docetaxel/Cisplatin/5-FU/Gemcitabine/ Camptothecin | H460, A549, H1650 (lung cancer) | All drugs showed increased IC-50 in 3D. | Caspase-3 is decreased in 3D. Drugs could not penetrated into cells in 3D and apoptosis was decreased. | Godugu et al.[107] |