Table 1.
Characterization of established drug-resistant human cancer cell lines
| Cells | Methods for induction of drug resistance | Cross resistance | Mechanisms of drug resistance | Ref. |
| Ovarian cancer A2780 Parental cells |
Continuous incremental drug selection | No ABCB1 expression | Vaidyanathan et al.[9] | |
| Olaparib resistant A2780 (A2780olapR) | Olaparib (1-20 μM) (37-fold resistant to olaparib) |
No cross resistance to paclitaxel | Higher ABCB1 expression (≥ 10-fold) | |
| Paclitaxel resistant A2780 (A2780pacR) | Paclitaxel (3 nM-2 mM) (7-fold resistant to paclitaxel) |
Cross-resistance to olaparib (37-fold) | Relative ABCB1 expression (≥ 50-fold) | |
| Colon cancer HCT116 Parental cells HCT116-s |
Continuously exposed to SN-38 (1-15 nM) | HCT116-SN6 and -SN50 were resistant to irinotecan and topotecan | Growth rate was slower in HCT116-SN50 than in HCT116-SN6 | Candeil et al.[10] |
| HCT116-SN6 HCT116-SN50 |
Growing in 10 nM SN-38 Growing in 15 nM SN-38 |
Only HCT116-SN50 was resistant to mitoxantrone and doxorubicin | Mechanism not identified Overexpression of ABCG2 |
|
| Colon cancer S1 (parental cells) S1-IR20 (irinotecan resistant, 48-fold) |
S1-IR20 established after 3-5 cycles of exposure to 0.5 mM irinotecan | S1-IR20, cross-resistant to SN-38 (RR = 47), topotecan (41), and mitoxantrone (37) | Overexpression of ABCG2 protein, but not ABCB1 or ABCC1. No change in Top1 protein | Wu et al.[11] |
| Colon cancer S1 (parental cells) S1-B1-20 (bisantrene resistant) S1-M1-80 (mitoxantrone resistant) |
S1-B1-20 by exposure to 20 mM bisantrene; S1-M1-80 by exposure to increasing concentrations of mitoxantrone | S1-B1-20 (RR) resistance: mitoxantrone (111), daunorubicin (38), vinblastine (167), paclitaxel (285), and topotecan (3) S1-M1-80 (RR): mitoxantrone (35,100), and topotecan (680) |
Higher ABCB1 level (14-fold) in S1-B1-20 and higher ABCG2 level (> 42,000-fold) in S1-M1-80 | Litman et al.[12] |
| HeLa cells (parental cells) Hvr1-1 cells: vinblastine (12) Hvr10-6 cells: vinblastine (166) Hvr100-6 cells: vinblastine (498) |
HeLa cells exposed to vinblastine (1, 10, and 100 nM) in a stepwise manner | Hvr100-6 (RR): doxorubicin (52), vincristine (327), paclitaxel (4145) Not resistant to platinum derivatives |
Higher level of ABCB1, but not ABCC1, in fluorescence-activated cell sorter analysis. ABCC1 and ABCG2 mRNA levels were comparable to those in HeLa cells | Takara et al.[13] |
| A bone osteosarcoma cell line, Saos-2 ABCG2 #4 clone |
cDNA-mediated ABCG2 expression in Saos-2 cells | ABCG2#4 (RR) resistant to irinotecan (168) and SN-38 (18) | ABCG2 | Wierdl et al.[14] |
| An ovarian carcinoma cell line, IFROV1 T8 cells (52-fold topotecan resistant) MX3 cells (11-fold mitoxantrone resistant) |
The T8 cell line was developed by exposure to increasing topotecan concentrations (24-240 nM) The MX3 cell line survived after 72 h exposure to 170 nM mitoxantrone |
T8 cells, resistant (RR) to SN-38 (176) and mitoxantrone (11) MX3 cells, resistant to topotecan (14) and SN-38 (44) |
Overexpression of breast cancer resistance protein, or ABCG2 | Maliepaard et al.[15] |
| Me32a-T22/2L: an immortalized fibroblast from a Menkes disease patient | Me32a/pCMB117: Me32a-T22/2L transfected with ATP7A cDNA | Me32a/pCMB117 was resistant to (RR) to SN-38 (43), irinotecan (13), paclitaxel (94), vincristine (70), and doxorubicin (13) | Overexpression of ATP7A protein in Me32a/pCMB117 (14) compared with Me32a-T22/2L | Owatari et al.[16] |
| Doxorubicin-resistant MCF-7 sublines | Resistant cells induced by low-dose doxorubicin Acetylated histone H3, RNA polymerase II was enriched to the proximal ABCG2 promoter region |
Degree of doxorubicin resistance ranged 1.3-3.6-fold | Increased ABCG2 expression Epigenetic alteration was observed in the resistant sublines |
Calcagno et al.[17] |
| Colon cancer S1-B1-80 cells |
S1-M1-80 was established by maintenance in the presence of increasing concentrations of mitoxantrone | An HuR protein that binds to AU-rich mRNA elements by enhancing their stability. Low miR-519c expression is correlated with high HuR and ABCG2 expression | Increased ABCG2 expression Epigenetic mechanism is likely to be involved |
To et al.[18] |
RR: Relative resistance compared to wild type cells.