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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]
  1. The table shows authors that compared effects in 2D and 3D cell cultures in the same article.